Clinical manifestations of Lyme disease

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease and motor neurone disease (MND), is a specific disease that causes the death of neurons which control voluntary muscles. ALS is characterized by stiff muscles, muscle twitching, and gradually worsening weakness due to muscles decreasing in size. This results in difficulty in speaking, swallowing, and eventually breathing.

ALS represents a very heterogeneous condition. There are limited data indicating that in small portion of patients with ALS Lyme disease may represent a leading driving force.

References:
ALSUntangled Group. ALS untangled No. 17: “when ALS is lyme”. Amyotroph Lateral Scler. 2012 Sep;13(5):487-91.

ALSUntangled Group. ALSUntangled update 1: investigating a bug (Lyme Disease) and a drug (Iplex) on behalf of people with ALS. Amyotroph Lateral Scler. 2009 Aug;10(4):248-50.

Halperin JJ1, Kaplan GP, Brazinsky S, Tsai TF, Cheng T, Ironside A, Wu P, Delfiner J, Golightly M, Brown RH, et al. Immunologic reactivity against Borrelia burgdorferi in patients with motor neuron disease. Arch Neurol. 1990 May;47(5):586-94.

Qureshi M1, Bedlack RS, Cudkowicz ME. Lyme disease serology in amyotrophic lateral sclerosis. Muscle Nerve. 2009 Oct;40(4):626-8.

Aphasia is an inability to comprehend and formulate language because of dysfunction in specific brain regions. Aphasia can cause impairments in speech and language modalities. To be diagnosed with aphasia, a person’s speech or language must be significantly impaired in one (or several) of the four communication modalities following acquired brain injury or have significant decline over a short time period (progressive aphasia). The four communication modalities are auditory comprehension, verbal expression, reading and writing, and functional communication.

The difficulties of people with aphasia can range from occasional trouble finding words to losing the ability to speak, read, or write; intelligence, however, is unaffected. Aphasia also affects visual language such as sign language. In contrast, the use of formulaic expressions in everyday communication is often preserved. One prevalent deficit in the aphasias is anomia, which is a deficit in word finding ability.

Mild form of aphasia also known as “brain fog” is a common manifestation of chronic Lyme disease.

References:
Sokolov AA, Lienhard R, Du Pasquier R, Erard V. Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia. Ann Emerg Med. 2015 Jul;66(1):60-4.

Ataxia is a neurological sign consisting of lack of voluntary coordination of muscle movements that includes gait abnormality. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum. Ataxia can be limited to one side of the body, which is referred to as hemiataxia.

Ataxia is a relatively uncommon manifestation of Lyme disease and is mainly seen in pediatric population.

References:
Arav-Boger R, Crawford T, Steere AC, Halsey NA. Cerebellar ataxia as the presenting manifestation of Lyme disease. Pediatr Infect Dis J. 2002 Apr;21(4):353-6.

Bertholon P, Cazorla C, Carricajo A, Oletski A, Laurent B. Bilateral sensorineural hearing loss and cerebellar ataxia in the case of late stage Lyme disease. Braz J Otorhinolaryngol. 2012 Dec;78(6):124.

Erol I, Saygı S, Alehan F. Acute cerebellar ataxia in a pediatric case of Lyme disease and a review of literature. Pediatr Neurol. 2013 May;48(5):407-10.

Lopez MD, Wise C. Acute ataxia in a 4-year-old boy: a case of Lyme disease neuroborreliosis. Am J Emerg Med. 2008 Nov;26(9):1069.e5-6.

Bell’s palsy is a type of facial paralysis that results in an inability to control the facial muscles on the affected side. Symptoms can vary from mild to severe. They may include muscle twitching, weakness, or total loss of the ability to move one or rarely both sides of the face. Other symptoms include drooping of the eyelid, a change in taste, pain around the ear, and increased sensitivity to sound.

Bell’s palsy occurs due to a malfunction of the facial nerve (VII cranial nerve), which controls the muscles of the face. Facial palsy is typified by inability to control movement in the facial muscles. The paralysis is of the infranuclear/lower motor neuron type.

The facial nerve controls a number of functions, such as blinking and closing the eyes, smiling, frowning, lacrimation, salivation, flaring nostrils and raising eyebrows. It also carries taste sensations from the anterior two-thirds of the tongue, via the chorda tympani nerve (a branch of the facial nerve). Because of this, people with Bell’s palsy may present with loss of taste sensation in the anterior 2/3 of the tongue on the affected side.

Although the facial nerve innervates the stapedial muscles of the middle ear (via the tympanic branch), sound sensitivity and dysacusis are hardly ever clinically evident.

People diagnosed with Bell’s palsy may experience various neurological symptoms including facial tingling, moderate or severe headache/neck pain, memory problems, balance problems, ipsilateral limb paresthesias, ipsilateral limb weakness, and a sense of clumsiness that are unexplained by facial nerve dysfunction.

Facial nerve palsy is common in patients with Lyme disease.

Lyme disease is the leading cause of Bell’s palsy in children.

Recent data indicate that the use of oral corticosteroids in patients with Lyme-driven Bell’s palsy is associated with worse long-term facial function outcomes.

References:
Eiffert H, Karsten A, Schlott T, Ohlenbusch A, Laskawi R, Hoppert M, Christen HJ.Acute peripheral facial palsy in Lyme disease — a distal neuritis at the infection site. Neuropediatrics. 2004 Oct;35(5):267-73.

Halperin JJ. Facial nerve palsy associated with lyme disease. Muscle Nerve. 2003 Oct;28(4):516-7.

Hashimoto Y, Takahashi H, Kishiyama K, Sato Y, Nakao M, Miyamoto K, Iizuka H.Lyme disease with facial nerve palsy: rapid diagnosis using a nested polymerase chain reaction-restriction fragment length polymorphism analysis. Br J Dermatol. 1998 Feb;138(2):304-9.

Ho K, Melanson M, Desai JA. Bell palsy in lyme disease-endemic regions of canada: a cautionary case of occult bilateral peripheral facial nerve palsy due to Lyme disease. CJEM. 2012 Sep;14(5):321-4.

Jowett N, Gaudin RA, Banks CA, Hadlock TA. Steroid use in Lyme disease-associated facial palsy is associated with worse long-term outcomes. Laryngoscope. 2016 Sep 6. doi: 10.1002/lary.26273.

Smouha EE, Coyle PK, Shukri S. Facial nerve palsy in Lyme disease: evaluation of clinical diagnostic criteria. Am J Otol. 1997 Mar;18(2):257-61.

Tveitnes D, Øymar K, Natås O. Acute facial nerve palsy in children: how often is it lyme borreliosis? Scand J Infect Dis. 2007;39(5):425-31.

Dementia is a broad category of brain diseases that cause a long term and often gradual decrease in the ability to think and remember that is great enough to affect a person’s daily functioning. Other common symptoms include emotional problems, problems with language, and a decrease in motivation. A person’s consciousness is usually not affected. A dementia diagnosis requires a change from a person’s usual mental functioning and a greater decline than one would expect due to aging.

Various chronic infections, including Lyme disease, have been proposed as triggers of dementia. However, the exact mechanism explaining the link of the infectious process to dementia is still poorly determined.

In clinical settings, it is well recognized that a coexistent Lyme disease can aggravate symptoms of dementia.

References:
Blanc F, Philippi N, Cretin B, Kleitz C, Berly L, Jung B, Kremer S, Namer IJ, Sellal F, Jaulhac B, de Seze J. Lyme neuroborreliosis and dementia. J Alzheimers Dis. 2014;41(4):1087-93.

Meer-Scherrer L, Chang Loa C, Adelson ME, Mordechai E, Lobrinus JA, Fallon BA, Tilton RC. Lyme disease associated with Alzheimer’s disease. Curr Microbiol. 2006 Apr;52(4):330-2.

Miklossy J. Biology and neuropathology of dementia in syphilis and Lyme disease. Handb Clin Neurol. 2008;89:825-44.

Miklossy J, Khalili K, Gern L, Ericson RL, Darekar P, Bolle L, Hurlimann J, Paster BJ.Borrelia burgdorferi persists in the brain in chronic lyme neuroborreliosis and may be associated with Alzheimer disease. J Alzheimers Dis. 2004 Dec;6(6):639-49.

Nitrini R. Clinical and therapeutic aspects of dementia in syphilis and Lyme disease. Handb Clin Neurol. 2008;89:819-23.

Waniek C, Prohovnik I, Kaufman MA, Dwork AJ. Rapidly progressive frontal-type dementia associated with Lyme disease. J Neuropsychiatry Clin Neurosci. 1995 Summer;7(3):345-7.

A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves. In turn, the reduction in conduction ability causes deficiency in sensation, movement, cognition, or other functions depending on which nerves are involved.

Demyelinating diseases are traditionally classified in two kinds: demyelinating myelinoclastic diseases and demyelinating leukodystrophic diseases. In the first group a normal and healthy myelin is destroyed by a toxic, chemical or autoimmune substance. In the second group, myelin is abnormal and degenerates.

In the most known example, multiple sclerosis, there is good evidence that the body’s own immune system is at least partially responsible. Acquired immune system cells called T-cells are known to be present at the site of lesions. Other immune system cells called Macrophages (and possibly Mast cells as well) also contribute to the damage.

Lyme disease is associated with myelinoclastic demyelinating group of diseases.

References:
Grisold W, Vass A. Antibiotic responsive demyelinating neuropathy related to Lyme disease. Neurology. 2010 Mar 16;74(11):935.

Muley SA, Parry GJ. Antibiotic responsive demyelinating neuropathy related to Lyme disease. Neurology. 2009 May 19;72(20):1786-7.

Reik L Jr, Smith L, Khan A, Nelson W. Demyelinating encephalopathy in Lyme disease. Neurology. 1985 Feb;35(2):267-9.

Savely G. Neuralgia and demyelinating plaques: MS or lyme disease? Adv Nurse Pract. 2005 Sep;13(9):20.

Sterman AB, Nelson S, Barclay P. Demyelinating neuropathy accompanying Lyme disease. Neurology. 1982 Nov;32(11):1302-5.

Encephalomyelitis is a general term for inflammation of the brain and spinal cord. Encephalomyelitis was described in association with Lyme disease.

References:
Fallon BA, Nields JA. Acute disseminated encephalomyelitis. J Neuropsychiatry Clin Neurosci. 1998 Summer;10(3):366-7.

Lock G, Berger G, Gröbe H. [Neuroborreliosis: progressive encephalomyelitis with cerebral vasculitis]. Monatsschr Kinderheilkd. 1989 Feb;137(2):101-4.

Rocha R1, Lisboa L, Neves J, García López M, Santos E, Ribeiro A. Neuroborreliosis presenting as acute disseminated encephalomyelitis. Pediatr Emerg Care. 2012 Dec;28(12):1374-6.

Idiopathic intracranial hypertension AKA pseudotumor cerebri , is a neurological disorder that is characterized by increased intracranial pressure (pressure around the brain) in the absence of a tumor or other diseases. The main symptoms are stroke-like headache, nausea, and vomiting, as well as pulsatile tinnitus (sounds perceived in the ears, with the sound occurring in the same rhythm as the pulse), double vision and other visual symptoms. If untreated, it may lead to swelling of the optic disc in the eye, which can progress to vision loss.

The diagnosis of idiopathic intracranial hypertension is confirmed by the demonstrating of papilledema, negative brain MRI or CT scan in a combination with lumbar puncture demonstrating increased opening pressure.

Idiopathic intracranial hypertension is a common but frequently misdiagnosed manifestation of Lyme disease/neuroborreliosis.

References:
Castaldo JE, Griffith E, Monkowski DH. Pseudotumor cerebri: early manifestation of adult Lyme disease. Am J Med. 2008 Jul;121(7):e5-6.

Härtel C, Schilling S, Neppert B, Tiemer B, Sperner J. Intracranial hypertension in neuroborreliosis. Dev Med Child Neurol. 2002 Sep;44(9):641-2.

Jacobson DM, Frens DB. Pseudotumor cerebri syndrome associated with Lyme disease. Am J Ophthalmol. 1989 Jan 15;107(1):81-2.

Kan L, Sood SK, Maytal J. Pseudotumor cerebri in Lyme disease: a case report and literature review. Pediatr Neurol. 1998 May;18(5):439-41.

Nord JA, Karter D. Lyme disease complicated with pseudotumor cerebri. Clin Infect Dis. 2003 Jul 15;37(2):e25-6.

Ramgopal S, Obeid R, Zuccoli G, Cleves-Bayon C, Nowalk A. Lyme disease-related intracranial hypertension in children: clinical and imaging findings. J Neurol. 2016 Mar;263(3):500-7.

Meningitis is an acute inflammation of the protective membranes, meninges, covering the brain and spinal cord. The most common symptoms are fever, headache and neck stiffness. Other symptoms include confusion or altered consciousness, vomiting, and an inability to tolerate light or loud noises. Young children often exhibit only nonspecific symptoms, such as irritability, drowsiness, or poor feeding.

Meningitis can be life-threatening because of the inflammation’s proximity to the brain and spinal cord; therefore, the condition is classified as a medical emergency.

Meningitis can lead to serious long-term consequences such as deafness, epilepsy, hydrocephalus, or cognitive deficits, especially if not treated quickly.

The diagnosis of meningitis is typically confirmed by the spinal tap and subsequent analysis of cerebrospinal fluid (CSF). All cases of acute meningitis are divided into two categories: 1) septic meningitis when a specific microorganism is isolated from the CSF or less frequently from the peripheral blood and 2)aseptic meningitis when no microorganisms are isolated.

Lyme disease typically presents in the form of aseptic meningitis. Acute meningitis is much more common in children than in adults. In contrast, chronic lymphocytic meningitis is more common in adults than in children.

The diagnosis of Lyme-associated meningitis is based on detection of Borrelia-specific antibodies in CSF.

References:
Banarer M, Cost K, Rychwalski P, Bryant KA. Chronic lymphocytic meningitis in an adolescent. J Pediatr. 2005 Nov;147(5):686-90.

Coyle PK. Chronic Meningitis. Curr Treat Options Neurol. 2000 Jul;2(4):375-387.

Djukic M, Schmidt-Samoa C, Lange P, Spreer A, Neubieser K, Eiffert H, Nau R, Schmidt H. Cerebrospinal fluid findings in adults with acute Lyme neuroborreliosis. J Neurol. 2012 Apr;259(4):630-6.

Garro AC, Rutman MS, Simonsen K, Jaeger JL, Chapin K, Lockhart G. Prevalence of Lyme meningitis in children with aseptic meningitis in a Lyme disease-endemic region. Pediatr Infect Dis J. 2011 Nov;30(11):990-2.

Tuerlinckx D, Bodart E, Garrino MG, de Bilderling G. Clinical data and cerebrospinal fluid findings in Lyme meningitis versus aseptic meningitis. Eur J Pediatr. 2003 Mar;162(3):150-3.

Tveitnes D, Natås OB, Skadberg Ø, Øymar K. Lyme meningitis, the major cause of childhood meningitis in an endemic area: a population based study. Arch Dis Child. 2012 Mar;97(3):215-20.

Normal pressure hydrocephalus is a type of brain malfunction caused by expansion of the lateral cerebral ventricles and distortion of the fibers in the corona radiata. The typical symptoms of normal pressure hydrocephalus are urinary incontinence, dementia, and gait disturbance. Lyme disease is associated with a secondary type on normal pressure hydrocephalus. Typically, the diagnosis of normal pressure hydrocephalus is confirmed by the brain CT scan or MRI.

References:
Aboul-Enein F1, Kristoferitsch W. Normal pressure hydrocephalus or neuroborreliosis? Wien Med Wochenschr. 2009;159(1-2):58-61.

Bremell D, Säll C, Gisslén M, Hagberg L. Lyme neuroborreliosis in HIV-1 positive men successfully treated with oral doxycycline: a case series and literature review. J Med Case Rep. 2011 Sep 19;5:465.

Danek A, Uttner I, Yoursry T, Pfister HW. Lyme neuroborreliosis disguised as normal pressure hydrocephalus. Neurology. 1996 Jun;46(6):1743-5.

Mokry M, Flaschka G, Kleinert G, Kleinert R, Fazekas F, Kopp W. Chronic Lyme disease with an expansive granulomatous lesion in the cerebellopontine angle. Neurosurgery. 1990 Sep;27(3):446-51.

Schnorf H, Albani C. Hydrocephalus complicating chronic Borrelia burgdorferi meningitis. Eur J Neurol. 1995 Nov;2(5):508-9.

Parkinsonism is a clinical syndrome characterized by tremor at rest, bradykinesia, rigidity, and postural instability. Parkinsonism shares symptoms found in Parkinson’s disease, from which it is named; but parkinsonism is a symptom complex, and differs from Parkinson’s disease which is a progressive neurodegenerative illness. The neurodegenerative condition Parkinson’s disease is the most common cause of parkinsonism.

Usually classified as a movement disorder, Parkinson’s disease also gives rise to several non-motor types of symptoms such as sensory deficits, cognitive difficulties, and sleep problems.

The motor symptoms of the disease result from the death of cells in the substantia nigra, a region of the midbrain. This results in not enough dopamine in these areas. The reason for this cell death is poorly understood, but involves the build-up of proteins into Lewy bodies in the neurons.

Parkinsonism and Parkinson’s disease were described in association with Lyme disease. However, the published data are very limited. Based on our clinic statistics, we believe that parkinsonism is not an uncommon manifestation of untreated chronic Lyme disease.

References:
Bu XL, Wang X, Xiang Y, Shen LL, Wang QH, Liu YH, Jiao SS, Wang YR, Cao HY, Yi X, Liu CH, Deng B, Yao XQ, Xu ZQ, Zhou HD, Wang YJ. The association between infectious burden and Parkinson’s disease: A case-control study. Parkinsonism Relat Disord. 2015 Aug;21(8):877-81.

Cassarino DS1, Quezado MM, Ghatak NR, Duray PH. Lyme-associated parkinsonism: a neuropathologic case study and review of the literature. Arch Pathol Lab Med. 2003 Sep;127(9):1204-6.

Patel R, Larnard J, Poowanawittayakom N, Glew R. 1800: Atypical Lyme Meningitis With Parkinson Disease-Like Manifestations. Crit Care Med. 2016 Dec;44(12 Suppl 1):525.

Peripheral neuropathy is damage to or disease affecting nerves, which may impair sensation, movement, gland or organ function, or other aspects of health, depending on the type of nerve affected. Neuropathy affecting just one nerve is called “mononeuropathy” and neuropathy involving multiple nerves in roughly the same areas on both sides of the body is called “symmetrical polyneuropathy” or simply “polyneuropathy.” When two or more (typically just a few, but sometimes many) separate nerves in disparate areas of the body are affected it is called “mononeuritis multiplex,” “multifocal mononeuropathy,” or “multiple mononeuropathy.”

Peripheral neuropathy may be chronic (a long-term condition where symptoms begin subtly and progress slowly) or acute (sudden onset, rapid progress, and slow resolution). Acute neuropathies demand urgent diagnosis. Motor nerves (that control muscles), sensory nerves, or autonomic nerves (that control automatic functions such as heart rate, body temperature, and breathing) may be affected. More than one type of nerve may be affected at the same time. Peripheral neuropathies may be classified according to the type of nerve predominantly involved, or by the underlying cause.

Neuropathy may cause painful cramps, fasciculations (fine muscle twitching), muscle loss, bone degeneration, and changes in the skin, hair, and nails. Additionally, motor neuropathy may cause impaired balance and coordination or, most commonly, muscle weakness; sensory neuropathy may cause numbness to touch and vibration, reduced position sense causing poorer coordination and balance, reduced sensitivity to temperature change and pain, spontaneous tingling or burning pain, or skin allodynia (severe pain from normally nonpainful stimuli, such as light touch); and autonomic neuropathy may produce diverse symptoms, depending on the affected glands and organs, but common symptoms are poor bladder control, abnormal blood pressure or heart rate, and reduced ability to sweat normally.

Lyme disease has been associated with both sensory and motor neuropathies. The exact mechanism triggering neuropathic processes in Lyme patients is still obscure. Among the potential explanations are borrelia-induced autoantibodies damaging peripheral nerves and inflammation of the blood vessels (vasculitis) feeding the nerves and causing insufficient nerve blood supply.

References:
Adams HB, Blasko GA, DiDomenico LA. An unusual case of bilaterally symmetrical neuropathic osteoarthropathy of the midfoot as a result of lyme disease-induced peripheral neuropathy: a case report. Foot Ankle Int. 2002 Feb;23(2):155-7.

Alaedini A, Latov N. Antibodies against OspA epitopes of Borrelia burgdorferi cross-react with neural tissue. J Neuroimmunol. 2005 Feb;159(1-2):192-5.

Dotevall L, Eliasson T, Hagberg L, Mannheimer C. Pain as presenting symptom in Lyme neuroborreliosis. Eur J Pain. 2003;7(3):235-9.

Dupeyron A, Lecocq J, Jaulhac B, Isner-Horobeti ME, Vautravers P, Cohen-Solal J, Sordet C, Kuntz JL. Sciatica, disk herniation, and neuroborreliosis. A report of four cases. Joint Bone Spine. 2004 Sep;71(5):433-7.

Kindstrand E, Nilsson BY, Hovmark A, Nennesmo I, Pirskanen R, Solders G, Asbrink E. Polyneuropathy in late Lyme borreliosis – a clinical, neurophysiological and morphological description. Acta Neurol Scand. 2000 Jan;101(1):47-52.

Mygland A, Skarpaas T, Ljøstad U. Chronic polyneuropathy and Lyme disease. Eur J Neurol. 2006 Nov;13(11):1213-5.

Rupprecht TA, Elstner M, Weil S, Pfister HW. Autoimmune-mediated olyneuropathy triggered by borrelial infection? Muscle Nerve. 2008 Jun;37(6):781-5.

Thaisetthawatkul P, Logigian EL. Peripheral nervous system manifestations of lyme borreliosis. J Clin Neuromuscul Dis. 2002 Jun;3(4):165-71.

Seizures are changes in the brain’s electrical activity. The outward effect can vary from uncontrolled jerking movement (tonic-clonic seizure) to as subtle as a momentary loss of awareness (absence seizure).

The signs and symptoms of seizures vary depending on the type. The most common type of seizure is convulsive (60%). Two-thirds of these begin as focal seizures and become generalized while one third begin as generalized seizures. The remaining 40% of seizures are non-convulsive, an example of which is absence seizure.

Seizures have been described in patients with Lyme disease. However, the frequency and specific type of seizures affecting Lyme patients are still poorly defined.

References:
Markeljević J, Sarac H, Rados M. Tremor, seizures and psychosis as presenting symptoms in a patient with chronic lyme neuroborreliosis (LNB). Coll Antropol. 2011 Jan;35 Suppl 1:313-8.

Stroke or cerebrovascular accident is a pathological condition when poor blood flow to the brain results in cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. They result in part of the brain not functioning properly. Signs and symptoms of a stroke may include an inability to move or feel on one side of the body, problems understanding or speaking, feeling like the world is spinning, or loss of vision to one side among others. Signs and symptoms often appear soon after the stroke has occurred. If symptoms last less than one or two hours it is known as a transient ischemic attack (TIA). Hemorrhagic strokes may also be associated with a severe headache. The symptoms of a stroke can be permanent. Long-term complications may include pneumonia or loss of bladder control.

Lyme disease has been associated with stroke in various age groups. Two leading mechanisms link Lyme disease and stroke: 1)inflammation of the cerebral blood vessels known as cerebral vasculitis and 2)increased blood coagulability due to borrelia-induced anti-phospolipid antibodies.

References:
Allen NM, Jungbluth H. Lyme Neuroborreliosis: A Potentially Preventable Cause of Stroke. J Pediatr. 2016 Mar;170:334-e1.

Almoussa M, Goertzen A, Fauser B, Zimmermann CW. Stroke as an Unusual First Presentation of Lyme Disease. Case Rep Neurol Med. 2015;2015:389081.

Lebas A, Toulgoat F, Saliou G, Husson B, Tardieu M. Stroke due to lyme neuroborreliosis: changes in vessel wall contrast enhancement. J Neuroimaging. 2012 Apr;22(2):210-2.

Li S, Vytopil M, Hreib K, Craven DE. Lyme disease presenting as multiple ischaemic strokes. Pract Neurol. 2015 Aug;15(4):284-8.

Reik L Jr. Stroke due to Lyme disease. Neurology. 1993 Dec;43(12):2705-7.

Wittwer B, Pelletier S, Ducrocq X, Maillard L, Mione G, Richard S. Cerebrovascular Events in Lyme Neuroborreliosis. J Stroke Cerebrovasc Dis. 2015 Jul;24(7):1671-8.

Zajkowska J, Garkowski A, Moniuszko A, Czupryna P, Ptaszyńska-Sarosiek I, Tarasów E, Ustymowicz A, Łebkowski W, Pancewicz S. Vasculitis and stroke due to Lyme neuroborreliosis – a review. Infect Dis (Lond). 2015 Jan;47(1):1-6.

Hemiparesis is unilateral paresis, that is, weakness of the entire left or right side of the body. Depending on the type of hemiparesis diagnosed, different bodily functions can be affected. People with hemiparesis often have difficulties maintaining their balance due to limb weaknesses leading to an inability to properly shift body weight. This makes performing everyday activities such as dressing, eating, grabbing objects, or using the bathroom more difficult. Hemiparesis with origin in the lower section of the brain creates a condition known as ataxia, a loss of both gross and fine motor skills, often manifesting as staggering and stumbling. Pure Motor Hemiparesis, a form of hemiparesis characterized by sided weakness in the leg, arm, and face, is the most commonly diagnosed form of hemiparesis.

Hemiparesis is a relatively rare manifestation of Lyme disease.

References:
Sokolov AA, Lienhard R, Du Pasquier R, Erard V. Acute Lyme Neuroborreliosis With Transient Hemiparesis and Aphasia. Ann Emerg Med. 2015 Jul;66(1):60-4.

Transverse myelitis is a neurological condition in which the spinal cord is inflamed. The inflammation damages nerve fibers, and causes them to lose their myelin coating leading to decreased electrical conductivity in the central nervous system. Transverse implies that the inflammation extends across the entire width of the spinal cord. Partial transverse myelitis and partial myelitis are terms used to define inflammation of the spinal cord that affects part of the width of the spinal cord.

The signs and symptoms of transverse myelitis depend on the area of spine involved:

Cervical: If the upper cervical cord is involved, all four limbs may be involved and there is risk of respiratory paralysis (cervical nerve segments C3, 4, 5 innervate the abdominal diaphragm). Lesions of the lower cervical (C5–T1) region will cause a combination of upper and lower motor neuron signs in the upper limbs, and exclusively upper motor neuron signs in the lower limbs.

Thoracic: A lesion of the thoracic spinal cord (T1–12) will produce upper motor neuron signs in the lower limbs, presenting as a spastic diplegia. This is the most common location of the lesion, and therefore most individuals will have weakness of the lower limbs.

Lumbar: A lesion of the lower part of the spinal cord (L1–S5) often produces a combination of upper and lower motor neuron signs in the lower limbs.

Symptoms include weakness and numbness of the limbs, deficits in sensation and motor skills, dysfunctional sphincter activities, and dysfunction of the autonomic nervous system. Sensory symptoms of transverse myelitis may include a sensation of pins and needles traveling up from the feet. Back pain can occur at the level of the inflamed segment of the spinal cord. The degree and type of sensory loss will depend upon the extent of the involvement of the various sensory tracts, but there is often a “sensory level” (at the sensory segmental level of the spinal cord below which sensation to pain or light touch is impaired). Motor weakness occurs due to involvement of the pyramidal tracts and mainly affects the muscles that flex the legs and extend the arms. Involvement of the autonomic nervous system is common and frequently leads to impaired function of the bladder and bowel and can also lead to episodes of high blood pressure.

Transverse myelitis is a relatively rare manifestation of Lyme disease and predominantly seen in children affected by the disease.

References:
Bigi S, Aebi C, Nauer C, Bigler S, Steinlin M. Acute transverse myelitis in Lyme neuroborreliosis. Infection. 2010 Oct;38(5):413-6.

Khan S, Singh N, Dow A, Ramirez-Zamora A. Pediatric Acute Longitudinal Extensive Transverse Myelitis Secondary to Neuroborreliosis. Case Rep Neurol. 2015 Jul 29;7(2):162-6.

Koc F, Bozdemir H, Pekoz T, Aksu HS, Ozcan S, Kurdak H. Lyme disease presenting as subacute transverse myelitis. Acta Neurol Belg. 2009 Dec;109(4):326-9.

Acrodermatitis chronica atrophicans is a skin manifestation of the late stage of Lyme disease and manifest in the form of asymmetrical inflammatory skin lesions on convex surfaces of the limbs with an atrophic course. This unusual progressive fibrosing skin process is caused by an ongoing active infection with Borrelia. It begins with an inflammatory stage characterized by bluish red discoloration and cutaneous swelling and concludes several months or years later with an atrophic phase. Sclerotic skin plaques may also develop.

Jessner-Kanof lymphocytic infiltration of the skin (JKLIS) is a chronic benign cutaneous disease characterized by asymptomatic non-scaly erythematous papules or plaques on the face and neck. Onset usually occurs between 30 and 50 years of age. Cutaneous lesions are mainly localized on the back, face, neck, shoulders, arms, and hands (sun-exposed skin). Their diameter usually varies between 2 mm and 2 cm. They consist of annular, pink or red papules, sometimes resulting in plaques. No follicular plugging or atrophy appears on the surface of the lesions. The lesions may be singular (approximately 15% of cases) or multiple. When multiple, they are often grouped with an arciform disposition. The lesions may remain unchanged for several months. Onset or exacerbation of the lesions may occur after sun exposure. In general, the lesions are asymptomatic, but they may be sometimes associated with a burning sensation or pruritus. They may spontaneously disappear, without resulting scars.

The diagnosis is based on examination of a routine skin biopsy sample, revealing nodular perivascular or periadnexal lymphocytes, and dermal infiltration under a normal or only slightly modified epidermis. Direct immunofluorescence analyses are usually negative (absence of lupus band test).

Borrelial lymphocytoma or lymphocytoma cutis is one of the most common types of cutaneous B cell pseudolymphoma. It seems to be more common in children than in adults and appears to be one of the rarest of the dermatological manifestations of Lyme disease. Borrelial lymphocytoma typically presents as a bluish-red plaque or nodule that varies from one to a few centimetres in diameter. The most common sites of borrelial lymphocytoma include the nipple, genital area, and earlobe. Lesions are typically noted 30-45 days after a tick bite and appear most frequently during the months of August and September. The infected individuals may not recall or give a history of a tick bite.

Lymphomas that arise in organs or tissues outside of the lymphatic system are called extranodal lymphomas. When extranodal lymphomas originate in the skin (comprising 18 percent of all extranodal lymphomas and five percent of all non-Hodgkin lymphomas), and there is no evidence of disease outside of the skin, they are called primary cutaneous lymphomas. Primary cutaneous B-cell lymphomas (CBCLs) occur when the lymphoma cells originate in B-cells. CBCLs are nearly always indolent (slow-growing). They may appear on the skin as a reddish rash, lump, or nodule and may have a slightly raised and smooth appearance. The disease tends to go away and then return on the skin, but it rarely develops into a disease that affects other areas of the body. Nearly 50 percent of patients diagnosed with CBCL experience a recurrence after an initial complete response to treatment. Prognosis is usually very good.

The eosinophilic fasciitis (EF) is a rare connective tissue disease characterized by symmetrical and painful swelling with a progressive induration and thickening of the skin and soft tissues. The diagnosis of EF is often based on the association of characteristic skin or subcutaneous abnormalities and a thickened fascia with an inflammatory infiltration, mostly composed of lymphocytes and eosinophils. A peripheral eosinophilia is frequently present, but is not mandatory for the EF diagnosis. The diagnosis might be helped by a muscle magnetic resonance imaging which typically may evidence increased signal intensity within the fascia and marked fascia enhancement after gadolinium administration at the acute phase of the disease.

Erythema chronicum migrans also known as “bull’s eye rash” refers to the rash often seen in the early stage of Lyme disease. It can appear anywhere from one day to one month after a tick bite. This rash represents an actual skin infection with Borrelia burgdorferi. Multiple painless EM rashes may occur, indicating disseminated infection.

Erythema multiforme is a type of erythema that is mediated by deposition of immune complexes (mostly IgM-bound complexes) in the superficial microvasculature of the skin and oral mucous membrane. Erythema multiforme may be present within a wide spectrum of severity. Erythema multiforme minor represents a localized eruption of the skin with minimal or no mucosal involvement. The papules evolve into pathognomonic target or iris lesions that appear within a 72-hour period and begin on the extremities (see the following image). Lesions remain in a fixed location for at least 7 days and then begin to heal.

Granuloma annulare (GA) is a benign inflammatory dermatosis. Granuloma annulare is relatively common disease that occurs in all age groups, but it is rare in infancy. Granuloma annulare is characterized clinically by dermal papules and annular plaques. Aside from the visible rash, granuloma annulare is usually asymptomatic. Sometimes the rash may burn or itch. Patients usually notice a ring of small, firm papules over the backs of the forearms, hands or feet, often centered on joints or knuckles. The papules are caused by the clustering of T cells below the skin. These papules start as very small, pimple looking bumps, which spread over time from that size to dime, quarter, half-dollar size and beyond. Occasionally, multiple rings may join into one. Rarely, granuloma annulare may appear as a firm nodule under the skin of the arms or legs. It also occurs on the sides and circumferential at the waist and without therapy can continue to be present for many years. Outbreaks continue to develop at the edges of the aging rings.

Granuloma annulare, microscopically, consists of dermal epithelioid histiocytes around a central zone of mucin – a so-called palisaded granuloma.

The panniculitides represent a group of heterogeneous inflammatory diseases that involve the subcutaneous fat. The specific diagnosis of these diseases requires histopathologic study because different panniculitides usually show the same clinical appearance, which consists of subcutaneous erythematous nodules on the lower extremities. However, the histopathologic study of panniculitis is difficult because of an inadequate clinicopathologic correlation, and the changing evolutionary nature of the lesions means that biopsy specimens are often taken from late-stage lesions, which results in nonspecific histopathologic findings. In addition, large-scalpel incisional biopsies are required. It must be accepted that all panniculitides are somewhat mixed because the inflammatory infiltrate involves both the septa and lobules; however, in general the differential diagnosis between a mostly septal and a mostly lobular panniculitis is straightforward at scanning magnification.

Lichen sclerosus et atrophicus also known as lichen sclerosus is a chronic inflammatory dermatosis that results in white plaques with epidermal atrophy and scarring. Lichen sclerosus has both genital and extragenital presentations.

Women are more commonly affected than men (10 to 1 ratio), particularly around and after menopause, but younger women or girls may also develop the disease. The condition most commonly occurs on the vulva and around the anus with ivory-white elevations that may be flat and glistening. There may be marked itching or the condition may be without any symptoms. There may also be thinning and shrinkage of the genital area that may make coitus, urination, and defecation painful.

In males, the disease may take the form of whitish thickening of the foreskin, which cannot be retracted easily (phimosis). In contrast to women, there is no perianal involvement. In men, this genital involvement has traditionally been known as balanitis xerotica obliterans.

On the non-genital skin, the disease may manifest as porcelain-white spots with small visible plugs inside the orifices of hair follicles or sweat glands on the surface. Thinning of the skin may also occur.

There is evidence that lichen sclerosus can be associated with thyroid disease.

Morphea, also known as “localized scleroderma”, or “circumscribed scleroderma”, is a disease that manifests in the form of isolated patches of hardened skin due to excessive collagen deposition. Morphea is most often presents as macules or plaques a few centimeters in diameter, but also may occur as bands or in guttate lesions or nodules. Morphea includes specific conditions ranging from very small plaques only involving the skin to widespread disease causing functional and cosmetic deformities.

Borrelia burgdorferi can cause scleroderma-like lesions of the manifesting in the form of confluent areas of skin fibrosis. Typically, these lesions affect upper and lower extremities as well as face.

Urticarial vasculitis is an eruption of erythematous wheals that clinically resemble urticaria but histologically show changes of leukocytoclastic vasculitis. Urticarial vasculitis may be divided into normocomplementemic and hypocomplementemic variants. Both subsets can be associated with systemic symptoms (eg, angioedema, arthralgias, abdominal or chest pain, fever, pulmonary disease, renal disease, episcleritis, uveitis, and Raynaud phenomenon). The hypocomplementemic form more often is associated with systemic symptoms and has been linked to connective-tissue disease (ie, systemic lupus erythematosus [SLE]). Diagnosis is confirmed with the identification of at least two conditions from: venulitis on skin biopsy, arthritis, ocular inflammation, abdominal pain or positive C1q antibodies to immune complexes.

Diarrhea is a relatively rare manifestation of Lyme disease and other tick-borne illnesses. Diagnosis of borrelia-associated diarrhea quite often represents a very difficult diagnostic task. In our practice, several cases of borrelia-associated diarrhea responded well to cholestyramine.

References:
Reisinger EC, Fritzsche C, Krause R, Krejs GJ. Diarrhea caused by primarily non-gastrointestinal infections. Nat Clin Pract Gastroenterol Hepatol. 2005 May;2(5):216-22.

Acute and chronic Lyme disease can trigger elevation of liver enzymes and various forms (morphological or histological) of hepatitis. Based on our personal experience, borrelia associated elevation of liver enzymes and hepatitis do respond to appropriate anti-microbial therapy. In clinical practice, borrelia-associated elevation of liver enzymes and hepatitis should be differentiated from the drug-induced processes.

References:
Bessonova EN, Lesniak OM, Podymova SD, Bazarnyĭ VV. [Clinical characteristics and risk factors of hepatic damage in lyme borrheliosis]. Klin Med (Mosk). 2000;78(4):36-40.

Chavanet P, Pillon D, Lancon JP, Waldner-Combernoux A, Maringe E, Portier H. Granulomatous hepatitis associated with Lyme disease. Lancet. 1987 Sep 12;2(8559):623-4.

Edwards KS, Kanengiser S, Li KI, Glassman M. Lyme disease presenting as hepatitis and jaundice in a child. Pediatr Infect Dis J. 1990 Aug;9(8):592-3.

Horowitz HW, Dworkin B, Forseter G, Nadelman RB, Connolly C, Luciano BB, Nowakowski J, O’Brien TA, Calmann M, Wormser GP. Liver function in early Lyme disease. Hepatology. 1996 Jun;23(6):1412-7.

Kazakoff MA, Sinusas K, Macchia C. Liver function test abnormalities in early Lyme disease. Arch Fam Med. 1993 Apr;2(4):409-13.

Muslmani M, Gilson M, Sudre A, Juvin R, Gaudin P. [Lyme disease with hepatitis and corticosteroids: a case report]. Rev Med Interne. 2012 Jun;33(6):339-42.

Nicolas X, Granier H, Zagnoli F, Bellard S.[Lyme borreliosis hepatitis]. Presse Med. 2002 Feb 23;31(7):319.

Schoen RT. Relapsing or reinfectious lyme hepatitis. Hepatology. 1989 Feb;9(2):335-6.

Sinusas K, Kazakoff MA, Macchia C. Hepatitis associated with Lyme disease. J Am Board Fam Pract. 1992 Nov-Dec;5(6):635-7.

Zanchi AC, Gingold AR, Theise ND, Min AD.Necrotizing granulomatous hepatitis as an unusual manifestation of Lyme disease. Dig Dis Sci. 2007 Oct;52(10):2629-32.

Gastroparesis, also called delayed gastric emptying, is a condition consisting of a paresis (partial paralysis) of the stomach, resulting in food remaining in the stomach for an abnormally long time. Normally, the stomach contracts to move food down into the small intestine for additional digestion. The vagus nerve controls these contractions. Gastroparesis may occur when the vagus nerve is damaged and the muscles of the stomach and intestines do not properly function. Food then moves slowly or stops moving through the digestive tract.

The most common symptoms of gastroparesis include chronic nausea, vomiting, abdominal pain, feeling fullness after eating small meals.

Since Lyme disease is known to affect vagus nerve function, gastroparesis and chronic nausea are relatively frequently seen in patients with Lyme disease.

The treatment of Lyme-associated gastroparesis requires complex therapy and may involve classical prokinetic drugs (metoclopramide, domperidone), macrolide antibiotics (erythromycin and azithromycin), baclofen as well as such herbal remedies as fennel extract and astragalus. In Europe, an herbal product Iberogast is gaining popularity as a natural substitution for pharmaceutical prokinetics.

References:
Ochoa Sangrador C, Gudino Curto P, Bajo Delgado AF, Hernández González N. [Probable neuroborreliosis with paralysis of hypoglossal and vagus nerves]. An Pediatr (Barc). 2014 Oct;81(4):267-9.

Pande H, Lacy BE, Crowell MD. Inflammatory causes of gastroparesis: report of five cases. Dig Dis Sci. 2002 Dec;47(12):2664-8.

Puri BK, Shah M, Monro JA, Kingston MC, Julu PO. Respiratory modulation of cardiac vagal tone in Lyme disease. World J Cardiol. 2014 Jun 26;6(6):502-6.

Chronic constipation is a common disease especially among the elderly population. Occasionally patients with no previous history of gastrointestinal disease develop severe chronic constipation, often refractory to conservative treatment. This condition is also called chronic intestinal pseudoobstruction and is often classified as idiopathic. Since the pathogenesis in some of these cases is due to a neuropathy involving the enteric nervous system, diseases that involve autonomic neuropathy, eg, diabetes mellitus, alcohol abuse, and paraneoplastic syndrome, are known causes chronic intestinal pseudoobstruction.

Since Lyme disease also targets enteric nervous system, it is not uncommon to see chronic constipation/intestinal pseudoobstraction in patients suffering from this ailment. In our practice, we see a good response of chronic constipation/intestinal pseudoobstraction to a combination of triphala, magnesium malate and linaclotide.

References:
Autschbach R, Zaremba A, Ulrich B. [Pseudo-obstruction of the colon following tick bite injury]. Chirurg. 1989 May;60(5):365-7.

Chatila R, Kapadia CR. Intestinal pseudoobstruction in acute Lyme disease: a case report. Am J Gastroenterol. 1998 Jul;93(7):1179-80.

Schefte DF, Nordentoft T. Intestinal Pseudoobstruction Caused by Chronic Lyme Neuroborreliosis. A Case Report. J Neurogastroenterol Motil. 2015 Jul 30;21(3):440-2.

Splenomegaly is an enlargement of the spleen. Clinically if a spleen is palpable, it means it is enlarged as it has to undergo at least twofold enlargement to become palpable. Symptoms of splenomegaly may include abdominal pain, chest pain, chest pain similar to pleuritic pain when stomach, bladder or bowels are full, back pain, early satiety due to splenic encroachment, or the symptoms of anemia due to accompanying cytopenia.

Splenomegaly is a relatively rare manifestation of Lyme disease.

References:
Cimmino MA, Azzolini A, Tobia F, Pesce CM. Spirochetes in the spleen of a patient with chronic Lyme disease. Am J Clin Pathol. 1989 Jan;91(1):95-7.

Nelson JA, Nemcek AA Jr. Vesicular rash, radicular pain, and splenomegaly in a patient with Lyme borreliosis. Clin Infect Dis. 1992 Jul;15(1):180-1.

At IFSMED, we have observed several patients with Lyme disease who were complaining of postexertional shortness of breath and eventually were diagnosed with dysfunction of diaphragm.

The diaphragm is a sheet of internal skeletal muscle that extends across the bottom of the thoracic cavity. The diaphragm separates the thoracic cavity containing the heart and lungs, from the abdominal cavity and performs an important function in respiration: as the diaphragm contracts, the volume of the thoracic cavity increases, and air is drawn into the lungs.

Diaphragmatic elevation at chest radiography will often be the first clue of dysfunction. Usually, the entire hemidiaphragm will be elevated in paralysis or weakness. With eventration, only a portion of a hemidiaphragm is elevated. Muscle atrophy and diaphragmatic thinning can be seen in some cases of dysfunction.

Another way of classifying diaphragmatic dysfunction is according to the involvement of one or both hemidiaphragms. Dysfunction can be unilateral or, less commonly, bilateral. Unilateral impairment is often asymptomatic and discovered incidentally on radiographic imaging. However, patients can be symptomatic and complain of dyspnoea on exertion. Patients with underlying lung disease are usually more symptomatic. Shortness of breath in the supine position or orthopnoea in particular can be present because of pressure from abdominal contents on the undersurface of the diaphragm. Pulmonary function tests show a restrictive pattern, which manifests as a reduction in total lung capacity and in vital capacity.

As opposed to unilateral diaphragmatic dysfunction, bilateral diaphragmatic dysfunction is usually symptomatic, often leading to respiratory failure. Hypoventilation that may result in hypercapnic respiratory failure with elevated arterial carbon dioxide tension (paCO2) is the hallmark of this condition. At this point, the accessory muscles of respiration will take over the role of the dysfunctional diaphragm.

Pulmonary fibrosis is a chronic disease in which scars are formed in the lung tissues, leading to serious breathing problems. Scar formation, the accumulation of excess fibrous connective tissue (the process called fibrosis), leads to thickening of the walls, and causes reduced oxygen supply in the blood. As a consequence patients suffer from perpetual shortness of breath.

Symptoms of pulmonary fibrosis are:

• Shortness of breath, particularly with exertion
• Chronic dry, hacking coughing
• Fatigue and weakness
• Chest discomfort including chest pain
• Loss of appetite and rapid weight loss

Pulmonary fibrosis is suggested by a history of progressive shortness of breath (dyspnea) with exertion. Sometimes fine aspiratory crackles can be heard at the lung bases on auscultation. A chest x-ray may or may not be abnormal, but high-resolution CT will frequently demonstrate abnormalities.

Based on our personal clinical observation, a small subset of patients with pulmonary fibrosis may have Lyme disease or more frequently RMSF (Rocky Mountain Spotted Fever) as associated illnesses or even triggers of fibrosis.

Sarcoidosis is an inflammatory disease in which granulomas, or clumps of inflammatory cells, form in various organs. The disease usually begins in the lungs, and less frequently in the skin or lymph nodes. Less commonly affected are the eyes, liver, heart, and brain. Any organ, however, can be affected. The signs and symptoms depend on the organ involved.

When it affects the lungs there may be wheezing, cough, shortness of breath, or chest pain.

Borrelia burgdorferi can be associated with sarcoidosis in genetically predisposed individuals. Those with affected family members are at greater risk. Diagnosis is partly based on signs and symptoms, which may be supported by biopsy. Findings that make it likely include large lymph nodes at the root of the lung on both sides, high blood calcium with a normal parathyroid hormone level, or elevated levels of angiotensin converting enzyme (ACE) in the blood.

Signs and Symptoms

The presentation in sarcoidosis varies with the extent and severity of organ involvement, as follows:

• Asymptomatic (incidentally detected on chest imaging): Approximately 5% of cases
• Systemic complaints (fever, anorexia): 45% of cases
• Pulmonary complaints (dyspnea on exertion, cough, chest pain, and hemoptysis [rare]): 50% of cases
• Löfgren syndrome (fever, bilateral hilar lymphadenopathy, and polyarthralgias)

Pulmonary findings on physical examination are as follows:

• Crackles may be audible
• Exertional oxygen desaturation may be present

Dermatologic manifestations may include the following:

• Erythema nodosum
• A lower-extremity panniculitis with painful, erythematous nodules (often with Löfgren syndrome)
• Lupus pernio (the most specific associated cutaneous lesion)
• Violaceous rash on the cheeks or nose (common)
• Maculopapular plaques (uncommon)

Ocular involvement, which may lead to blindness if untreated, may manifest as follows:

• Anterior or posterior granulomatous uveitis (most frequent)
• Conjunctival lesions and scleral plaques

Other possible manifestations are as follows:

• Osseous involvement
• Heart failure from cardiomyopathy (rare)
• Heart block and sudden death
• Lymphocytic meningitis (rare)
• Cranial nerve palsies and hypothalamic/pituitary dysfunction (rare)

Imaging studies for sarcoidosis are as follows:

• Chest radiography: Central to the evaluation
• Routine chest computed tomography (CT): Adds little to radiography
• High-resolution CT (HRCT) scanning of the chest: May be helpful; identifies active alveolitis versus fibrosis, and findings correlate with biopsy yield
• Gallium scans: Used infrequently; has low sensitivity and specificity, but may be helpful when the clinical picture remains confusing despite histologic evidence of noncaseating granulomas (eg, differentiating chronic hypersensitivity pneumonitis from sarcoidosis)

Atrioventricular block (AV block) is a type of heart block in which the conduction between the atria and ventricles of the heart is impaired. Under normal conditions, the sinoatrial node (SA node) in the atria sets the pace for the heart, and these impulses travel down to the ventricles. In an AV block, this message does not reach the ventricles or is impaired along the way. The ventricles of the heart have their own pacing mechanisms, which can maintain a lowered heart rate in the absence of SA stimulation.

Lyme disease can cause AV block which in most of the cases represents a reversible problem.

References:
Bhattacharya IS, Dweck M, Francis M. Lyme carditis: a reversible cause of complete atrioventricular block. J R Coll Physicians Edinb. 2010 Jun;40(2):121-2.

Dobbs LB, Mugmon MA. Wenckebach responsive to cephalosporins – it must be Lyme carditis. J Community Hosp Intern Med Perspect. 2013 Dec 17;3(3-4).

Forrester JD, Mead P. Third-degree heart block associated with lyme carditis: review of published cases. Clin Infect Dis. 2014 Oct;59(7):996-1000.

Karmacharya P, Aryal MR. Heart stopping tick. World J Cardiol. 2013 May 26;5(5):148-50.

Semmler D, Blank R, Rupprecht H. Complete AV block in Lyme carditis: an important differential diagnosis. Clin Res Cardiol. 2010 Aug;99(8):519-26.

Shah P, Mithawala P, Bajaj S, Virk H, Bikkina M. Third-degree heart block as initial presentation of Lyme disease. Acta Cardiol. 2015 Dec;70(6):744-5.

Shenthar J, Shetty SB, Krishnamurthy D. Diagnosis not to be missed: Lyme carditis, rare but reversible cause of complete atrioventricular block. Indian Heart J. 2014 Nov-Dec;66(6):723-6.

Timmer SA, Boswijk DJ, Kimman GP, Germans T. A case of reversible third-degree AV block due to Lyme carditis. J Electrocardiol. 2016 Jul-Aug;49(4):519-21.

Wenger N, Pellaton C, Bruchez P, Schläpfer J. Atrial fibrillation, complete atrioventricular block and escape rhythm with bundle-branch block morphologies: an exceptional presentation of Lyme carditis. Int J Cardiol. 2012 Sep 20;160(1):e12-4.

Congestive heart failure occurs when the heart is unable to pump sufficiently to maintain blood flow to meet the body’s needs. Signs and symptoms commonly include shortness of breath, excessive tiredness, and leg swelling. The shortness of breath is usually worse with exercise, while lying down, and may wake the person at night. A limited ability to exercise is also a common feature.

The condition is diagnosed based on the history of the symptoms and a physical examination with confirmation by echocardiography.

Although Lyme disease was described in association with congestive heart failure, the actual prevalence of Lyme disease among patients with congestive heart failure is unknown.

References:
Koene R, Boulware DR, Kemperman M, Konety SH, Groth M, Jessurun J, Eckman PM. Acute heart failure from lyme carditis. Circ Heart Fail. 2012 Mar 1;5(2):e24-6.

Sonnesyn SW, Diehl SC, Johnson RC, Kubo SH, Goodman JL. A prospective study of the seroprevalence of Borrelia burgdorferi infection in patients with severe heart failure. Am J Cardiol. 1995 Jul 1;76(1):97-100.

Stanek G, Klein J, Bittner R, Glogar D. Borrelia burgdorferi as an etiologic agent in chronic heart failure? Scand J Infect Dis Suppl. 1991;77:85-7.

Dilated cardiomyopathy (DCM) is a condition in which the heart becomes enlarged and cannot pump blood efficiently. The decreased heart function can affect the lungs, liver, and other body systems.

DCM is one of the cardiomyopathies, a group of diseases that affect primarily the heart muscle. In DCM a portion of the myocardium is dilated, often without any obvious cause. Left or right ventricular systolic pump function of the heart is impaired, leading to progressive heart enlargement via ventricular hypertrophy and ventricular dilation, a process called ventricular remodeling.

Dilated cardiomyopathy is the most common form of non-ischemic cardiomyopathy. It occurs more frequently in men than in women, and is most common between the ages of 20 and 60 years. About one in three cases of congestive heart failure is due to dilated cardiomyopathy. Dilated cardiomyopathy also occurs in children.

Dilated cardiomyopathy may not cause symptoms significant enough to impact on quality of life. A minority of people can experience significant symptoms. These might include: shortness of breath, syncope, chest pain. A person suffering from dilated cardiomyopathy may have an enlarged heart, with pulmonary edema and an elevated jugular venous pressure and a low pulse pressure. Signs of mitral and tricuspid regurgitation may be present. A fast heart rate with no change during the respiratory cycle may also be found.

Dilated cardiomyopathy has been described in association with Lyme disease. However, the actual prevalence of Lyme disease in patients with dilated cardiomyopathy is still unknown.

References:
Cuffe MS. Lyme disease: an active agent in dilated cardiomyopathy? Am Heart J. 1999 Aug;138(2 Pt 1):198-9.

Kuchynka P, Palecek T, Havranek S, Vitkova I, Nemecek E, Trckova R, Berenová D, Krsek D, Podzimkova J, Fikrle M, Danek BA, Linhart A. Recent-onset dilated cardiomyopathy associated with Borrelia burgdorferi infection. Herz. 2015 Sep;40(6):892-7.

Kubánek M, Šramko M, Berenová D, Hulínská D, Hrbáčková H, Malušková J, Lodererová A, Málek I, Kautzner J. Detection of Borrelia burgdorferi sensu lato in endomyocardial biopsy specimens in individuals with recent-onset dilated cardiomyopathy. Eur J Heart Fail. 2012 Jun;14(6):588-96.

Bartůnek P, Gorican K, Mrázek V, Varejka P, Veiser T, Hercogová J, Hulínská D, Janovská D. Lyme borreliosis infection as a cause of dilated cardiomyopathy. Prague Med Rep. 2006;107(2):213-26.

Bartůnĕk P, Gorican K, Veiser T, Táborský M, Hulínská D. Significance of Borrelia infection in development of dilated cardiomypathy (a pilot study). Prague Med Rep. 2007;108(4):339-47.

Gasser R, Dusleag J, Fruhwald F, Klein W, Reisinger E. Early antimicrobial treatment of dilated cardiomyopathy associated with Borrelia burgdorferi. Lancet. 1992 Oct 17;340(8825):982.

Gasser R, Dusleag J, Reisinger E, Stauber R, Feigl B, Pongratz S, Klein W, Furian C, Pierer K. Reversal by ceftriaxone of dilated cardiomyopathy Borrelia burgdorferi infection. Lancet. 1992 May 9;339(8802):1174-5.

Endocarditis is an inflammation of the inner layer of the heart, the endocardium. It usually involves the heart valves. Other structures that may be involved include the interventricular septum, the chordae tendineae, the mural endocardium, or the surfaces of intracardiac devices. Endocarditis is characterized by lesions, known as vegetations, which is a mass of platelets, fibrin, microcolonies of microorganisms, and scant inflammatory cells. In the subacute form of infective endocarditis, the vegetation may also include a center of granulomatous tissue, which may fibrose or calcify.

The diagnosis of endocarditis is based on clinical features, investigations such as an echocardiogram, and blood cultures demonstrating the presence of endocarditis-causing microorganisms. Signs and symptoms include: fever, chills, sweating, malaise, weakness, anorexia, weight loss, splenomegaly, flu-like feeling, cardiac murmur, heart failure, petechia of anterior trunk, Janeway’s lesions, etc.

References:
Hidri N, Barraud O, de Martino S, Garnier F, Paraf F, Martin C, Sekkal S, Laskar M, Jaulhac B, Ploy MC. Lyme endocarditis. Clin Microbiol Infect. 2012 Dec;18(12):E531-2.

Kaell AT, Redecha PR, Elkon KB, Golightly MG, Schulman PE, Dattwyler RJ, Kaell DL, Inman RD, Christian CL, Volkman DJ. Occurrence of antibodies to Borrelia burgdorferi in patients with nonspirochetal subacute bacterial endocarditis. Ann Intern Med. 1993 Dec 1;119(11):1079-83.

Kaell AT, Volkman DJ, Gorevic PD, Dattwyler RJ. Positive Lyme serology in subacute bacterial endocarditis. A study of four patients. JAMA. 1990 Dec 12;264(22):2916-8.

Rudenko N, Golovchenko M, Mokrácek A, Piskunová N, Ruzek D, Mallatová N, Grubhoffer L. Detection of Borrelia bissettii in cardiac valve tissue of a patient with endocarditis and aortic valve stenosis in the Czech Republic. J Clin Microbiol. 2008 Oct;46(10):3540-3.

Myocarditis, also known as inflammatory cardiomyopathy, is inflammation of the heart muscle. Symptoms can include shortness of breath, chest pain, decreased ability to exercise, and an irregular heartbeat. The duration of problems can vary from hours to months. Complications may include heart failure due to dilated cardiomyopathy or cardiac arrest.

A diagnosis may be supported by an electrocardiogram (ECG), increased troponin, heart MRI, and occasionally a heart biopsy. An ultrasound of the heart is important to rule out other potential causes such as heart valve problems.

Lyme disease is one of the known causes of myocarditis.

References:
Costello JM, Alexander ME, Greco KM, Perez-Atayde AR, Laussen PC. Lyme carditis in children: presentation, predictive factors, and clinical course. Pediatrics. 2009 May;123(5):e835-41.

Fish AE, Pride YB, Pinto DS. Lyme carditis. Infect Dis Clin North Am. 2008 Jun;22(2):275-88.

Klein J, Stanek G, Bittner R, Horvat R, Holzinger C, Glogar D. Lyme borreliosis as a cause of myocarditis and heart muscle disease. Eur Heart J. 1991 Aug;12 Suppl D:73-5.

Maher B, Murday D, Harden SP. Cardiac MRI of Lyme disease myocarditis. Heart. 2012 Feb;98(3):264.

Manzoor K, Aftab W, Choksi S, Khan IA. Lyme carditis: sequential electrocardiographic changes in response to antibiotic therapy. Int J Cardiol. 2009 Oct 2;137(2):167-71.

Naik M, Kim D, O’Brien F, Axel L, Srichai MB. Images in cardiovascular medicine. Lyme carditis. Circulation. 2008 Oct 28;118(18):1881-4.

Rostoff P, Gajos G, Konduracka E, Gackowski A, Nessler J, Piwowarska W. Lyme carditis: epidemiology, pathophysiology, and clinical features in endemic areas. Int J Cardiol. 2010 Oct 8;144(2):328-33.

Scheffold N, Herkommer B, Kandolf R, May AE. Lyme carditis–diagnosis, treatment and prognosis. Dtsch Arztebl Int. 2015 Mar 20;112(12):202-8.

Pericarditis is inflammation of the pericardium (the fibrous sac surrounding the heart). Symptoms typically include sudden onset of sharp chest pain. The pain may also be felt in the shoulders, neck, or back. It is typically better sitting up and worse with lying down or breathing deep. Other symptoms may include fever, weakness, palpitations, and shortness of breath.

Substernal or left precordial pleuritic chest pain with radiation to the trapezius ridge (the bottom portion of scapula on the back), which is relieved by sitting up and bending forward and worsened by lying down (recumbent or supine position) or inspiration (taking a breath in), is the characteristic pain of pericarditis. The pain may resemble the pain of angina pectoris or heart attack, but differs in that pain changes with body position, as opposed to heart attack pain that is pressure-like, and constant with radiation to the left arm and/or the jaw. Other symptoms of pericarditis may include dry cough, fever, fatigue, and anxiety.

References:
Briant C, Roye K, Kutscher AH Jr. Pericarditis as a manifestation of Lyme disease.
J Emerg Nurs. 1997 Dec;23(6):525-9.

Bruyn GA, De Koning J, Reijsoo FJ, Houtman PM, Hoogkamp-Korstanje JA Lyme pericarditis leading to tamponade. Br J Rheumatol. 1994 Sep;33(9):862-6.

Guex-Crosier Y, Herbort CP. Recurrent uveitis, cystoid macular edema and pericarditis in Lyme disease. Ocul Immunol Inflamm. 1994;2(2):111-3.

Postural orthostatic tachycardia syndrome (POTS) is a condition in which a change from the supine position to an upright position causes an abnormally large increase in heart rate, called tachycardia.

The hallmark symptom of POTS is an increase in heart rate by at least 30 beats per minute within 10 minutes of assuming an upright position. For people aged between 12 and 19, the minimum increase for diagnosis is 40 beats per minute. This symptom is known as orthostatic (upright) tachycardia (fast heart rate). It occurs without any coinciding drop in blood pressure, as that would indicate orthostatic hypotension.
It is accompanied by other features of orthostatic intolerance—symptoms which develop in an upright position and are relieved by reclining. These orthostatic symptoms include palpitations, light-headedness, chest discomfort, shortness of breath, nausea, weakness or “heaviness” in the lower legs, blurred vision and cognitive difficulties. Symptoms may be exacerbated with prolonged sitting, prolonged standing, alcohol, heat, exercise, or eating a large meal.

In up to one third of people with POTS, fainting occurs in response to postural changes or exercise. Migraine-like headaches are common, sometimes with symptoms worsening in an upright position (orthostatic headache). Some people with POTS develop acrocyanosis, or blotchy, red/blue skin upon standing, especially over the feet (indicative of blood pooling).

POTS is also often accompanied by vasovagal syncope, with a 25% overlap being reported. There is significant overlap between POTS and chronic fatigue syndrome, with evidence of POTS in 25–50% of CFS cases. Fatigue and reduced exercise tolerance are prominent symptoms of both conditions, and dysautonomia may underlie both conditions.

Although the connection between POTS and Lyme disease has not been described extensively, in our clinic we this association quite frequently.

References:
Kanjwal K, Karabin B, Kanjwal Y, Grubb BP. Postural orthostatic tachycardia syndrome following Lyme disease. Cardiol J. 2011;18(1):63-6.

Noyes AM, Kluger J. A tale of two syndromes: Lyme disease preceding postural orthostatic tachycardia syndrome. Ann Noninvasive Electrocardiol. 2015 Jan;20(1):82-6.

Sudden cardiac death or cardiac arrest is a sudden stop in effective blood flow due to the failure of the heart to contract effectively. Symptoms include loss of consciousness and abnormal or absent breathing. If not treated within minutes, death usually occurs.

The most common cause of cardiac arrest is coronary artery disease. The initial heart rhythm is most often ventricular fibrillation. Cardiac arrest is sometimes preceded by certain symptoms such as fainting, fatigue, blackouts, dizziness, chest pain, shortness of breath, weakness, and vomiting. The arrest may also occur with no warning.

When the arrest occurs, the most obvious sign of its occurrence will be the lack of a palpable pulse in the person experiencing it (since the heart has ceased to contract, the usual indications of its contraction such as a pulse will no longer be detectable). Certain types of prompt intervention can often reverse a cardiac arrest, but without such intervention the event will almost always lead to death. Also, as a result of inadequate cerebral perfusion, the patient will quickly become unconscious and will have stopped breathing.

Cardiac arrest was described as a complication of Lyme disease.

References:

Centers for Disease Control and Prevention (CDC). Three sudden cardiac deaths associated with Lyme carditis – United States, November 2012-July 2013. MMWR Morb Mortal Wkly Rep. 2013 Dec 13;62(49):993-6.

Forrester JD, Meiman J, Mullins J, Nelson R, Ertel SH, Cartter M, Brown CM, Lijewski V, Schiffman E, Neitzel D, Daly ER, Mathewson AA, Howe W, Lowe LA, Kratz NR, Semple S, Backenson PB, White JL, Kurpiel PM, Rockwell R, Waller K, Johnson DH, Steward C, Batten B, Blau D, DeLeon-Carnes M, Drew C, Muehlenbachs A, Ritter J, Sanders J, Zaki SR, Molins C, Schriefer M, Perea A, Kugeler K, Nelson C, Hinckley A, Mead P; Centers for Disease Control and Prevention (CDC). Notes from the field: update on Lyme carditis, groups at high risk, and frequency of associated sudden cardiac death–United States. MMWR Morb Mortal Wkly Rep. 2014 Oct 31;63(43):982-3.

Muehlenbachs A, Bollweg BC, Schulz TJ, Forrester JD, DeLeon Carnes M, Molins C, Ray GS, Cummings PM, Ritter JM, Blau DM, Andrew TA, Prial M, Ng DL, Prahlow JA, Sanders JH, Shieh WJ, Paddock CD, Schriefer ME, Mead P, Zaki SR. Cardiac Tropism of Borrelia burgdorferi: An Autopsy Study of Sudden Cardiac Death Associated with Lyme Carditis. Am J Pathol. 2016 May;186(5):1195-205.

Acute kidney injury also known as acute renal failure, is an abrupt loss of kidney function that develops within 7 days. Its causes are numerous. Generally it occurs because of damage to the kidney tissue caused by decreased kidney blood flow (kidney ischemia) from any cause (e.g., low blood pressure), exposure to substances harmful to the kidney, an inflammatory process in the kidney, or an obstruction of the urinary tract that impedes the flow of urine. AKI is diagnosed on the basis of characteristic laboratory findings, such as elevated blood urea nitrogen and creatinine, or inability of the kidneys to produce sufficient amounts of urine.

References:
Jeandel C, Perret C, Blain H, Jouanny P, Penin F, Laurain MC. Rhabdomyolysis with acute renal failure due to Borrelia burgdorferi. J Intern Med. 1994 Feb;235(2):191-2.

Rolla D, Conti N, Ansaldo F, Panaro L, Lusenti T. Post-infectious glomerulonephritis presenting as acute renal failure in a patient with Lyme disease. J Renal Inj Prev. 2013 Nov 8;3(1):17-20.

Chronic kidney disease (CKD), also known as chronic renal disease, is progressive loss in kidney function over a period of months or years. The symptoms of worsening kidney function are not specific, and might include feeling generally unwell and experiencing a reduced appetite. Often, chronic kidney disease is diagnosed as a result of screening of people known to be at risk of kidney problems. This disease may also be identified when it leads to one of its recognized complications, such as cardiovascular disease, anemia, pericarditis or renal osteodystrophy (the latter included in the novel term CKD-MBD).

CKD is a long-term form of kidney disease; thus, it is differentiated from acute kidney disease (acute kidney injury) in that the reduction in kidney function must be present for over 3 months. CKD is an internationally recognized public health problem affecting 5–10% of the world population.

References:
Kwiatkowska E, Gołembiewska E, Ciechanowski K, Kędzierska K. Minimal-Change Disease Secondary to Borrelia burgdorferi Infection. Case Rep Nephrol. 012;2012:294532.

Manion BA. Lyme disease in chronic renal failure: CAPD therapy. ANNA J. 1990 Aug;17(4):320-1.

Cryoglobulinemia is a medical condition in which the blood contains large amounts of cryoglobulins – proteins (mostly immunoglobulins themselves) that become insoluble at reduced temperatures. Cryoglobulins typically precipitate at temperatures below normal body temperature (37 °C) and will dissolve again if the blood is heated. The precipitated clump can block blood vessels and cause kidney damage. Cryoglobulinemia can be associated with various infectious diseases including Lyme disease.

References:
Kirmizis D, Efstratiadis G. MPGN secondary to Lyme disease: the role of cryoglobulins. Clin Kidney J. 2013 Jun;6(3):349.

Steere AC, Hardin JA, Malawista SE. Erythema chronicum migrans and Lyme arthritis: cryoimmunoglobulins and clinical activity of skin and joints. Science. 1977 Jun 3;196(4294):1121-2.

Steere AC, Hardin JA, Ruddy S, Mummaw JG, Malawista SE. Lyme arthritis: correlation of serum and cryoglobulin IgM with activity, and serum IgG with remission. Arthritis Rheum. 1979 May;22(5):471-83.

IgA nephropathy, also known as IgA nephritis, or Berger disease, is a disease of the kidney (or nephropathy), specifically it is a form of glomerulonephritis or an inflammation of the glomeruli of the kidney.

IgA nephropathy is the most common glomerulonephritis worldwide. Primary IgA nephropathy is characterized by deposition of the IgA antibody in the glomerulus. In IgA nephropathy there is a slow progression to chronic kidney failure in 25–30% of cases during a period of 20 years.

The classic presentation (in 40–50% of the cases) is episodic hematuria. Groin pain can also occur. The gross hematuria resolves after a few days, though microscopic hematuria may persist. These episodes occur on an irregular basis every few months and in most patients eventually subsides, although it can take many years. Renal function usually remains normal, though rarely, acute kidney failure may occur (see below). This presentation is more common in younger adults. A smaller proportion (20-30%), usually the older population, have microscopic hematuria and proteinuria (less than 2 gram/day). These patients may not have any symptoms and are only clinically found if a physician decides to take a urine sample.

IgA nephropathy is the most common kidney disease associated with Lyme disease.

References:
Rolla D, Conti N, Ansaldo F, Panaro L, Lusenti T. Post-infectious glomerulonephritis presenting as acute renal failure in a patient with Lyme disease. J Renal Inj Prev. 2013 Nov 8;3(1):17-20.

Rollino C, Vischini G, Coppo R. IgA nephropathy and infections. J Nephrol. 2016 Aug;29(4):463-8.

Zachäus M. Mesangioproliferative IgA-nephritis in a patient with lyme borreliosis. MMW Fortschr Med. 2008 Mar 27;150(13):38-40.

Interstitial cystitis (IC), also known as bladder pain syndrome (BPS), is a type of chronic pain that affects the bladder. Symptoms include feeling the need to urinate right away, needing to urinate often, and pain with sex. The diagnosis is usually based on the symptoms after ruling out other conditions. Typically the urine culture is negative. Ulceration or inflammation maybe seen on cystoscopy. IC was described in association with Lyme disease.

References:
Haarala M, Kiiholma P, Nurmi M, Uksila J, Alanen A. The role of Borrelia burgdorferi in interstitial cystitis. Eur Urol. 2000 Apr;37(4):395-9.

Schwan TG, MacDonald AB. Interstitial cystitis and Borrelia burgdorferi. Ann Intern Med. 1989 Sep 15;111(6):537.

Membranoproliferative glomerulonephritis (“MPGN”), also known as mesangiocapillary glomerulonephritis, is a type of glomerulonephritis caused by deposits in the kidney glomerular mesangium and basement membrane (GBM) thickening, activating complement and damaging the glomeruli.

MPGN accounts for approximately 4% of primary renal causes of nephritic syndrome in children and 7% in adults.

Lyme disease can cause MPGN. The disease responds well to a combination of antibiotics and sorticosteroids.

References:
Kelly B, Finnegan P, Cormican M, Callaghan J. Lyme disease and glomerulonephritis. Ir Med J. 1999 Aug;92(5):372.

Kirmizis D, Efstratiadis G, Economidou D, Diza-Mataftsi E, Leontsini M, Memmos D. MPGN secondary to Lyme disease. Am J Kidney Dis. 2004 Mar;43(3):544-51.

Mc Causland FR, Niedermaier S, Bijol V, Rennke HG, Choi ME, Forman JP. Lyme disease-associated glomerulonephritis. Nephrol Dial Transplant. 2011 Sep;26(9):3054-6.

Chorioretinal folds are wrinkles or undulations in the choroid, Bruch’s membrane and retinal pigment epithelium. Distortion of the choroid (as a result of mechanical force and/or vascular occlusion) is thought to exert pressure on the relatively inflexible Bruch’s membrane, which is thrown into folds.

Retinal folds involve only the sensory retina, and are generally narrower than choroidal folds. They most commonly develop when a tractional force is exerted upon a focal area of the retina. The folds themselves may result in focal areas of blurring, distortion or loss of vision.

References:

Balcer LJ, Winterkorn JM, Galetta SL. Neuro-ophthalmic manifestations of Lyme disease. J Neuroophthalmol. 1997 Jun;17(2):108-21.

Karma A, Mikkilä H. Ocular manifestations and treatment of Lyme disease. Curr Opin Ophthalmol. 1996 Jun;7(3):7-12.

Lesser RL. Ocular manifestations of Lyme disease. Am J Med. 1995 Apr 24;98(4A):60S-62S.

Zaidman GW. The ocular manifestations of Lyme disease. Int Ophthalmol Clin. 1997 Spring;37(2):13-28.

Image source: http://onlinelibrary.wiley.com

Conjunctivitis, also known as pink eye, is inflammation of the outermost layer of the white part of the eye and the inner surface of the eyelid. It makes the eye appear pink or reddish. There may also be pain, burning, scratchiness, or itchiness. The affected eye may have increased tears or be “stuck shut” in the morning. Swelling of the white part of the eye may also occur. Conjunctivitis can affect one or both eyes.

References:

Flach AJ, Lavoie PE. Episcleritis, conjunctivitis, and keratitis as ocular manifestations of Lyme disease. Ophthalmology. 1990 Aug;97(8):973-5.

Mombaerts IM, Maudgal PC, Knockaert DC. Bilateral follicular conjunctivitis as a manifestation of Lyme disease. Am J Ophthalmol. 1991 Jul 15;112(1):96-7.

Image source: http://diseasesdoctor.com

Crystalline keratopathy is a condition in which crystals are deposited in the corneal epithelium and/or anterior stroma. Affected individuals frequently present to the ophthalmologist with symptoms of pain, decreased vision or photophobia.

Infectious crystalline keratopathy may occur with a bacterial infection including Lyme disease. Infection-related crystalline deposits have a fine branchlike shape, develop over time and may be associated with inflammation.

References:

Dietrich T, Geissdörfer W, Schlötzer-Schrehardt U, Holbach L, Schoerner C, Seitz B. Borrelia-associated crystalline keratopathy with intracorneal detection of Borrelia garinii by electron microscopy and polymerase chain reaction. Cornea. 2008 May;27(4):498-500. doi: 10.1097/ICO.0b013e318162a8f5.

Image source: http://www.ophthalmologyreview.org

Dacryoadenitis is inflammation of the lacrimal glands (the tear-producing glands).

Typical symptoms of dacryoadenitis include:
– Swelling of the outer portion of the upper lid, with possible redness and tenderness
– Pain in the area of swelling
– Excess tearing or discharge
– Swelling of lymph nodes in front of the ear

References:

Nieto JC, Kim N, Lucarelli MJ. Dacryoadenitis and orbital myositis associated with lyme disease. Arch Ophthaloml. 2008 Aug;126(8):1165-6.

Image source: http://www.healio.com

Scleritis is an inflammatory disease that affects the white outer coating of the eye, known as the sclera.There are three types of scleritis: diffuse scleritis (the most common), nodular scleritis, and necrotizing scleritis (the most severe). Scleritis may be the first symptom of onset of connective tissue disease.

The symptoms of scleritis include:
– Redness of the sclera and conjunctiva, sometimes changing to a purple hue
– Severe ocular pain, which may radiate to the temple or jaw. The pain is often described as deep or boring.
– Photophobia and tearing
– Decrease in visual acuity, possibly leading to blindness

Episcleritis is inflammation of the episclera, a less serious condition that seldom develops into scleritis. The pain of episcleritis is less severe than in scleritis. In hyperemia, there is a visible increase in the blood flow to the sclera (hyperaemia), which accounts for the redness of the eye. Unlike in conjunctivitis, this redness will not move with gentle pressure to the conjunctiva.

References:

Krist D, Wenkel H. Posterior scleritis associated with Borrelia burgdorferi (Lyme disease) infection. Ophthalmology. 2002 Jan;109(1):143-5.

Zaidman GW. Episcleritis and symblepharon associated with Lyme keratitis. Am J Ophthalmol. 1990 Apr 15;109(4):487-8.

Image source: Jane Goodwin BSc MSc

A swollen eyelid occurs when there is inflammation or excess fluid (edema) in the connective tissues surrounding the eye. Swollen eyes can be painful and non-painful, and affect both the upper and lower eyelids. Swollen eyelid is a relatively rare manifestation of Lyme disease.

References:

Murillo G, Ramírez B, Romo LA, Muñoz-Sanz A, Hileeto D, Calonge M. Oculopalpebral borreliosis as an unusual manifestation of Lyme disease. Cornea. 2013 Jan;32(1):87-90.

Image source: http://emedicalhub.com

Keratitis is a condition in which the eye’s cornea, the front part of the eye, becomes inflamed. The condition is often marked by moderate to intense pain and usually involves any of the following symptoms: pain, impaired eyesight, photophobia, red eye and a ‘gritty’ sensation.

References:

Alzaga Fernandez AG, Demirci H, Darnley-Fisch DA, Steen DW. Interstitial keratitis secondary to severe hidradenitis suppurativa: a case report and literature review. Cornea. 2010 Oct;29(10):1189-91.

Miyashiro MJ, Yee RW, Patel G, Ruiz RS. Lyme disease associated with unilateral interstitial keratitis. Cornea. 1999 Jan;18(1):115-6.

Zaidman GW. The ocular manifestations of Lyme disease. Int Ophthalmol Clin. 1997 Spring;37(2):13-28.

Image source: http://www.artisanoptics.com

Optic neuritis is a demyelinating inflammation of the optic nerve that can result in complete or partial loss of vision in one or both eyes.

Major symptoms are sudden loss of vision (partial or complete), sudden blurred or “foggy” vision, and pain of movement of the affected eye. Other early symptoms are reduced night vision, photophobia and red eyes. Many patients with optic neuritis may lose some of their color vision in the affected eye (especially red), with colors appearing subtly washed out compared to the other eye. Patients may also experience difficulties judging movement in depth which can be particular troublesome during driving or sport (Pulfrich effect). Likewise transient worsening of vision with increase of body temperature (Uhthoff’s phenomenon) and glare disability are a frequent complaint.

On medical examination the head of the optic nerve can easily be visualized by a slit lamp with high plus or by using direct ophthalmoscopy; however, frequently there is no abnormal appearance of the nerve head in optic neuritis (in cases of retrobulbar optic neuritis), though it may be swollen in some patients (anterior papillitis or more extensive optic neuritis).

Optic neuritis was described as a relatively rare complication of Lyme disease and chronic bartonellosis. In our practice, we do see one or two new cases of optic neuritis associated with Lyme disease every year.

References:

Blanc F, Ballonzoli L, Marcel C, De Martino S, Jaulhac B, de Seze J. Lyme optic neuritis. J Neurol Sci. 2010 Aug 15;295(1-2):117-9.

Gan JJ, Mandell AM, Otis JA, Holmuhamedova M, Perloff MD. Suspecting optic neuritis, diagnosing Bartonella cat scratch disease. Arch Neurol. 2011 Jan;68(1):122-6.

Herz AM1, Lahey JM. Images in clinical medicine. Optic neuritis due to Bartonella henselae infection. N Engl J Med. 2004 Jan 8;350(2):e1.

Sibony P, Halperin J, Coyle PK, Patel K. Reactive Lyme serology in optic neuritis. J Neuroophthalmol. 2005 Jun;25(2):71-82.

Träisk F, Lindquist L. Optic nerve involvement in Lyme disease. Curr Opin Ophthalmol. 2012 Nov;23(6):485-90.

Winward KE, Smith JL, Culbertson WW, Paris-Hamelin A. Ocular Lyme borreliosis. Am J Ophthalmol. 1989 Dec 15;108(6):651-7.

Image source: http://www.msunites.com

Orbital myositis is an inflammatory process that primarily involves the extraocular muscles and most commonly affects young adults in the third decade of life, with a female predilection. Clinical characteristics of orbital myositis include orbital and periorbital pain, ocular movement impairment, diplopia, proptosis, swollen eyelids, and conjunctival hyperemia. The most common presentation is acute and unilateral. However, chronic and recurrent cases may involve both orbits.

References:

Carvounis PE, Mehta AP, Geist CE. Orbital myositis associated with Borrelia burgdorferi (Lyme disease) infection. Ophthalmology. 2004 May;111(5):1023-8.

Fatterpekar GM, Gottesman RI, Sacher M, Som PM. Orbital Lyme disease: MR imaging before and after treatment: case report. AJNR Am J Neuroradiol. 2002 Apr;23(4):657-9.

Sauer A1, Speeg-Schatz C, Hansmann Y. Two cases of orbital myositis as a rare feature of lyme borreliosis. Case Rep Infect Dis. 2011;2011:372470.

Seidenberg KB, Leib ML. Orbital myositis with Lyme disease. Am J Ophthalmol. 1990 Jan 15;109(1):13-6.

Image source: https://understandingmyositis.org

Ptosis is a drooping or falling of the upper eyelid. The drooping may be worse after being awake longer, when the individual’s muscles are tired. If severe enough and left untreated, the drooping eyelid can cause other conditions, such as amblyopia or astigmatism.

Ptosis occurs due to dysfunction of the muscles that raise the eyelid or their nerve supply (oculomotor nerve for levator palpebrae superioris and sympathetic nerves for superior tarsal muscle). It can affect one eye or both eyes. and is more common in the elderly, as muscles in the eyelids may begin to deteriorate. One can, however, be born with ptosis. Ptosis is a relatively rare manifestation of Lyme disease.

References:

Goldberg S, Katz BZ. Lyme disease presenting as ptosis, conjunctivitis, and photophobia. Clin Pediatr (Phila). 2012 Feb;51(2):186-7.

Xu L, Winn BJ, Odel JG. Lyme-associated orbital inflammation presenting as painless subacute unilateral ptosis. J Neuroophthalmol. 2012 Sep;32(3):246-8.

Image source: http://www.imperialhealth.org

Retinal detachment is a disorder of the eye in which the retina separates from the layer underneath. Symptoms include an increase in the number of floaters, flashes of light, and worsening of the outer part of the visual field. This may be described as a curtain over part of the field of vision.

The mechanism most commonly involves a break in the retina that then allows the fluid in the eye to get behind the retina. A break in the retina can occur from a posterior vitreous detachment, injury to the eye, or inflammation of the eye. Lyme disease is another cause of unexplained retinal detachment.

References:

Bialasiewicz AA, Ruprecht KW, Naumann GO, Blenk H. Bilateral diffuse choroiditis and exudative retinal detachments with evidence of Lyme disease. Am J Ophthalmol. 1988 Apr 15;105(4):419-20.

Grinager HS, Krason DA, Olsen TW. Lyme disease: resolution of a serous retinal detachment and chorioretinal folds after antibiotic therapy. Retin Cases Brief Rep. 2012 Summer;6(3):232-4.

Koch F, Augustin AJ, Böker. Neuroborreliosis with retinal pigment epithelium detachments. Ger J Ophthalmol. 1996 Jan;5(1):12-5.

Image source: https://www.britannica.com

Retinal vasculitis is inflammation of the vascular branches of the retinal artery, caused either by primary ocular disease processes, or as a specific presentation of any systemic form of vasculitis.

Retinal vasculitis presents as painless, decrease of visual acuity (blurry vision), visual floaters, scotomas (dark spot in vision), decreased ability to distinguish colors, and metamorphopsia (disrtion of images such as linear images). Ophthalmic examination may reveal neovascularization (creation of new vessels in the retina), retinal vessel narrowing, retinal vessel cuffing, retinal hemorrhage, or possible vitritis (inflammation of the vitreous body) or choroiditis (inflammation of the choroid).

References:

Leys AM, Schönherr U, Lang GE, Naumann GO, Goubau P, Honore A, Valvekens F. Retinal vasculitis in Lyme borreliosis. Bull Soc Belge Ophtalmol. 1995;259:205-14.

Smith JL, Winward KE, Nicholson DF, Albert DW. Retinal vasculitis in Lyme borreliosis. J Clin Neuroophthalmol. 1991 Mar;11(1):7-15.

Image source: http://www.jcor.in

Retinitis is an inflammation of the retina in the eye. The symptoms of retinitis include loss of night vision, loss of peripheral vision, leading to tunnel vision, loss of central vision as well as loss of color vision. Retinitis is common in patients with Lyme disease and chronic bartonellosis.

References:

Gupta PK, Patel R, Bhatti MT. Neuroretinitis secondary to concurrent infection with cat scratch disease and lyme disease. Eye (Lond). 2009 Jul;23(7):1607.

Karma A, Stenborg T, Summanen P, Immonen I, Mikkilä H, Seppälä I. Long-term follow-up of chronic Lyme neuroretinitis. Retina. 1996;16(6):505-9.

Karma A, Pirttilä TA, Viljanen MK, Lähde YE, Raitta CM. Secondary retinitis pigmentosa and cerebral demyelination in Lyme borreliosis. Br J Ophthalmol. 1993 Feb;77(2):120-2.

Lesser RL, Kornmehl EW, Pachner AR, Kattah J, Hedges TR 3rd, Newman NM, Ecker PA, Glassman MI. Neuro-ophthalmologic manifestations of Lyme disease.
Ophthalmology. 1990 Jun;97(6):699-706.

Reed JB, Scales DK, Wong MT, Lattuada CP Jr, Dolan MJ, Schwab IR. Bartonella henselae neuroretinitis in cat scratch disease. Diagnosis, management, and sequelae. Ophthalmology. 1998 Mar;105(3):459-66.

Image source: http://eyewiki.org/Neuroretinitis

Uveitis is the inflammation of the uvea, the pigmented layer that lies between the inner retina and the outer fibrous layer composed of the sclera and cornea. The uvea consists of the middle layer of pigmented vascular structures of the eye and includes the iris, ciliary body, and choroid. Uveitis is an ophthalmic emergency and requires a thorough examination by an ophthalmologist and urgent treatment to control the inflammation.

Signs of uveitis include dilated ciliary vessels, presence of cells and flare in the anterior chamber, and keratic precipitates on the posterior surface of the cornea. In severe inflammation there may be evidence of a hypopyon. Old episodes of uveitis are identified by pigment deposits on lens, keratic precipitates and festooned pupil on dilation of pupil.

References:

Breeveld J, Kuiper H, Spanjaard L, Luyendijk L, Rothova A. Uveitis and Lyme borreliosis. Br J Ophthalmol. 1993 Aug;77(8):480-1.

Kimura K, Isogai E, Isogai H, Nishikawa T, Masuzawa T, Yoshikawa K, Kotake S, Ohno S, Fujii N. Prevalence of antibodies against Borrelia species in patients with unclassified uveitis in regions in which Lyme disease is endemic and nonendemic. Clin Diagn Lab Immunol. 1995 Jan;2(1):53-6.

Mahne J, Kranjc BS, Strle F, Ružić-Sabljić E, Arnež M. Panuveitis caused by Borrelia burgdorferi sensu lato infection. Pediatr Infect Dis J. 2015 Jan;34(1):102-4.

Mikkilä H, Seppälä I, Leirisalo-Repo M, Immonen I, Karma A. The etiology of uveitis: the role of infections with special reference to Lyme borreliosis. Acta Ophthalmol Scand. 1997 Dec;75(6):716-9.

Image source: http://infodiseases.com