Table 2.

Lyme disease: classical clinical features and treatment options

Clinical Stage	Incubation Period	Clinical Types	Cutaneous Features and Histology	Systemic Features	Treatment in Adults (for Children)
Stage 1	1-30 days (average 1-3 weeks)	Early localized or primary Lyme disease	• Erythema migrans (EM) • Histology is characterized by perivascular infiltrate of lymphohistiocytes with sparse interspersed plasma cells in the dermis. Neutrophils, macrophages, dermal edema, and panniculitis are infrequent.	Minor constitutional symptoms of fever, chills, fatigue, malaise, transient oligoarthralgia, myalgia, headache, neck stiffness.	Doxycycline, orally 100mg twice daily (4mg/kg/d divided in two doses in children aged ≥8 years, maximum dose - as in adults) or Cefuroxime axetil, orally 500mg twice daily (30mg/kg/d in two divided doses, maximum 500mg/dose) or Azithromycin, orally 500mg once daily (10mg/kg/d, maximum 500mg/day) or Amoxicillin, orally 500mg three times daily (50mg/kg/d in three divided doses)
Stage 2	Weeks to months (average 3-20 weeks)	Early disseminated Lyme disease	• Multiple EM, secondary EM • Borrelia lymphocytoma (BL) Histology of BL shows dense lymphocytic infiltrate with nodules and germinal centers in the dermis and subcutis	Multisystem involvement occurs as myalgia, migratory polyarticular enthesitis, arthralgia, lymphocytic meningitis (waxing and waning mild-to-severe headache, neck stiffness, photophobia), facial nerve palsy, encephalopathy (mild confusional state, disturbances in sleep, mood, memory and concentration, depression, irritability, and personality disorder), cardiac symptoms (chest pain, palpitations, dizziness, syncope, dyspnea, atrioventricular block)	Ceftriaxone, intravenous 2g/day (50-75mg/kg/day, maximum 2g/day) or Cefotaxime, intravenous 2g every 8 hourly (150-200mg/kg/day, maximum 6g/day, in three to four divided doses or Doxycycline, orally 200-400mg in two divided doses daily (4-8mg/kg/day, maximum 100-200mg/day, in two divided doses in children aged ≥8 years)
Stage 3	Months to years	Chronic or late Lyme disease	• Acrodermatitis chronica atrophicans. • Histologically, a dense patchy periappendageal and perivascular inflammatory infiltrate of lymphohistiocytes and plasma cells seen in the early inflammatory stage, while epidermal atrophy with normal subepidermal zone, lymphocytic and plasma cell-rich infiltrate in the sclerotic upper dermis with dilated blood vessels will feature in the late stage.	Joints symptoms: Mono or oligoarthritis without neurological involvement. Knee arthritis is the hallmark of chronic Lyme disease.	Oral antibiotics as used for erythema migrans. Symptomatic treatment.
			Neuropsychiatric symptoms: Encephalomyelitis, subacute encephalopathy, myelitis (in 50% of cases), Bannwarth syndrome, progressive spastic paraparesis or quadriparesis, fibromyalgia, peripheral neuropathy, cognitive and affective disorders Ocular symptoms: Follicular conjunctivitis, photophobia, macular edema, uveitis/iridocyclitis, retinal vasculitis, choroiditis, retinal vein occlusion, white dot syndrome, stromal keratitis, episcleritis Cardiac symptoms: Conduction defects, arrhythmias, myocarditis, pericarditis, postural orthostatic tachycardia syndrome	Intravenous antibiotics as used for early disseminated disease. Symptomatic treatment.

Remarks: (1) Treatment is recommended for 2-3 weeks. (2) For adults, prophylactic doxycycline in a single 200mg dose (4mg/kg of body weight or maximum up to 200mg in children aged ≥8 years) is recommended orally within 72 hours of tick removal when it had remained attached for 36 hours or longer, or when risk of infection is high as in endemic areas. (3) Doxycycline remains contraindicated in patients with doxycycline hypersensitivity, children aged <8 years, and pregnant and lactating women. (4) Bannwarth syndrome is characterized by late axonal neuropathy and radiculopathy with pleocytosis