Table 2.

Unusual observations in various types of leishmaniasis and possible causes.

Disease Manifestations	Typical Manifestation	Unusual Observations	Plausible Mechanisms
Visceral leishmaniasis (VL)	Irregular bouts of fever, weight loss, anaemia, enlargement of spleen and liver LDB (amastigotes) spread to internal organs such as bone marrow, liver, spleen and lymph nodes through systemic circulation	Gastrointestinal tract, pulmonary system, larynx and skin are involved in addition to liver, spleen and bone marrow in in both immunocompromised and immune-competent cases LDB (amastigotes) seen in myelocytes, plasma cells and adrenal gland	Unusual presentation of an outcome of compromised immune response due to intrinsic poor immune system, co-infection with HIV or other pathogens Immune senescence leads to VL in geriatric population resulting in multiple relapses
Post-kala-azar dermal leishmaniasis (PKDL)	Dermal sequela of VL usually caused by L. donovani as a polymorphic presentation of macular, papular or nodular rash on face, upper arms, trunks and other parts of the body	Monomorphic presentation including macular, papular or papulonodular forms Localized or disseminated including mucosal, xanthomatous, verrucous, papillomatous, hypertrophic, fibroid, atrophic and extensive tumorous forms Lymph node and nerve involvement without impaired sensation Mucosa of genitalia, anus, lingual, perioral and oral cavity involved Indurated annular plaques with central clearing, irregular in shape, soft and non-tender juicy-looking papules, ulcerated lesions as seen in the tumorous, eroded and non-tender plaque Ocular leishmaniasis caused by L. donovani or dermotropic spp. causing permanent damage to the eyes, developed as post-kala-azar leishmanial conjunctivitis and blepharitis or post-kala-azar anterior uveitis	Ulcerations possibly due to repeated trauma Change in immune response from Th2 to a combined Th1/Th2 pattern underlines ocular leishmaniasis Antiretroviral therapy induced immune reconstitution syndrome among HIV–VL co-infected patients
Cutaneous leishmaniasis (CL)	Localized lesions at site of bite with changing appearance and size with course of time Mostly painless, however, may be painful pertaining to their presence near joints or due to bacterial infection	Atypical in terms of infecting species, e.g., VL-causing leishmania species causing cutaneous manifestations and vice versa CL at unusual sites including lesions in submandibular region mimic parotid neoplasm, auricle of ear, eyelids, haired and bald scalp, palm or lips, genitals (glans penis, scrotum) Morphological variants of CL lesions including erysipeloid form; chronic zosteriform CL in covered body parts; sporotrichoid form predominantly in upper limbs; lupoid form; leishmaniasis recidivans in the Old World regions or leishmaniasis recidiva cutis in New World regions Disseminated maculopapular rashes post relapse of VL	Genetic variations including gene polymorphisms or intra-species hybridization Alterations in immune response Treatment responses
Mucocutaneous leishmaniasis (MCL)	Metastatic sequela of New World cutaneous infection Dissemination of parasites from the skin to the naso- oropharyngeal mucosa causing degeneration and ultimately leading to destruction of the nasal septum	Oral leishmaniasis with the primary lesion (erythematous and oedematous) without involvement of cutaneous tissue Lesions on perioral mucosa, oro-facial mucosa, nasal mucosa, pharyngeal mucosa and cartilage bone septum, uvula, gingiva, soft palate, tonsils and epiglottis Recurrent epistaxis or nasal obstruction Primary endonasal leishmaniasis, focal hard whitish lesions on true vocal cords Ulcer with punched-out appearance extending to lip, smooth and erythematous swelling of lips (chelitis), granulomatous disease of endolarynx and oedema of oral mucosa resembling neoplasm Sublingual leishmaniasis with pseudotumoral morphology, lingual leishmaniasis with lymphoid-like tissue swelling Ocular scleromalacia, lesions on the conjunctiva of upper and lower eyelid, Disseminated MCL	Inadequate treatment of CL lesions Co-infection with interspecies strains