L-5 Dermal Leishmaniasis:

• Cutaneous Manifestations of Parasitic Infections are covered in COM 5851 LEC 5, Integumentary System, by Cyril Blavo D.O., MS, MPH & TM, FACOP, Professor of Pediatrics and Public Health, Dr. Kiran C. Patel College of Osteopathic Medicine, Nova Southeastern University

Learning Objectives

• Recognize the cutaneous manifestations, epidemiology, unique characteristics, diagnosis, and treatment of specific parasitic diseases

Dermal Leishmaniasis

• Etiology is Leishmania donovani, a flagellated protozoan
• Infection transmission occurs through the bite of a female sandfly (Phlebotomus), which takes a blood meal
• Transmission can also occur vertically or through blood
• Vertebrate hosts are dogs and mammals, and is common in India
• Promastigotes (from sandfly bite on skin) transform into amastigotes
• Amastigotes settle in macrophages within the reticuloendothelial system (RES), becoming Leishmania Donovani bodies, which leads to inflammatory damage in the liver, bone marrow, and lymph nodes
• Dermal Leishmaniasis is aka = Post-kala azar
• Clinical manifestations of visceral Leishmaniasis (Kala Azar) are intermittent high fever, malaise, anorexia, night sweats, diarrhea, hepatosplenomegaly, lymphadenopathy, anemia, pancytopenia, and darkening of skin ("Black fever")
• Cutaneous manifestations (Post-Kala Azar Dermal Leishmaniasis) include hypopigmented macules turning into painless papules, then nodular lesions, and finally ulcers (Mimics Leprosy)
• Diagnostic tests include the Montenegro test (Leishmania skin test), microscopy of blood/tissue with culture, and PCR
• Diagnosis of Visceral Leishmaniasis is "Kala Azar" or "Black Fever" and Post-Kala Azar Dermal Leishmaniasis (PKDL)
• Management involves IV/IM Pentavalent Antimonials, such as Sodium stibogluconate or Meglumine antimonate
• Complications include secondary bacterial infection and disfigurement
• Prevention measures are insecticide spraying (against the sandfly), wearing protective clothing, and early detection and treatment

Cercarial Dermatitis (Schistosomiasis)

• Etiology is Schistosoma haematobium, Schistosoma mansoni, and Schistosoma japonicum (Helminth-Trematoda - Blood fluke); it causes Schistosomiasis (Bilharziasis)
• Epidemiology involves skin penetration by cercaria from freshwater snails
• Miracidia in snails transform into cercaria, which penetrate skin and cause pruritic dermatitis
• Enters blood, transforms to adult worm, migrates to venous plexus of bladder and mesenteric vessels of bowels
• Can also be caused by cercariae from animal trematodes that often infect birds
• Clinical manifestation produces inflammatory, pruritic, skin eruption on extremities and trunk ("swimmer's itch")
• Katayama Fever (fever, pruritic rash, cough, bronchospasm, lymphadenopathy, eosinophilia; hepatosplenomegaly); hematuria (Urinary Schistosomiasis) can also occur
• Diagnosis is History (Travel; snail-infested freshwater exposure & Physical exam (rash). Microscopy (urine-eggs; hematuria). Schistosomiasis (Bilharzia)
• Another term for Cercarial Dermatitis is "Swimmer's Itch" Urinary Schistosomiasis
• Management is Praziquantel
• Prevention is Proper disposal of urine and feces and avoiding wading in infested waters

Cutaneous Larva Migrans (Ancylostomiasis)

• Etiology includes Ancylostoma braziliense catis (Cats); Ancylostoma braziliense canis (Dogs), aka "Dog/Cat Hookworm", Nematode
• Epidemiology presents worldwide
• Dog/cats are definitive hosts that excrete larvae in stool, which end up in soil
• Rhabiditiform Larvae in Soil forms Filariform Larvae that penetrate human skin
• Larvae penetrate skin and form serpiginous tunnel of infective filariform larvae in skin
• Clinical manifestations: Severe pruritus, blisters, and a red growing, "Serpigenous rash" and can grow up to 1 to 2 centimeters per day
• Diagnosis is Clinical (H&P) for Cutaneous Larva Migrans (CLM)
• Management is Albendazole or Thiabendazole
• Complications are secondary bacterial skin infection
• Prevention measures are sanitation and wearing proper footwear

Onchocerciasis

• Etiology is Onchocerca volvulus (Nematode; Helminth)
• Epidemiology involves infection via bite of black fly (Simulium damnosum)
• Larvae enter Simulium bite wound; enters subcutaneous tissue -> adults develop -> forming Painless Skin Nodules
• Microfilariae are produced and released in blood causing host allergic and inflammatory reactions to adult worm and microfilariae
• Affects eyes, causes dermatitis and keratoconjunctivitis (eye inflammation and corneal clouding)
• Clinical manifestation in skin is pruritus; skin atrophy, fibrosis, pigmentation and Eyes: photophobia; blurred vision; blindness
• Diagnosis comes from microscopy (skin snip)
• Onchocerciasis produces Onchocercoma (subcutaneous lesion) and Corneal opacification, aka ocular Sclerosing Keratitis ("River Blindness")
• Management is Ivermectin
• Complications are secondary bacterial skin infection
• Prevention is vector control (Larvicide) and wearing protective clothing

Scabies

• Etiology is Sarcoptes scabeii (a mite)
• Transmission is via person-to-person contact via skin, clothing, towels or bedding
• It is highly contagious and common in children and the immunosuppressed
• Scabies mite bites and burrows through skin causing cutaneous burrows
• Eggs are deposited in burrows where adult mites mature; life cycle lasts 8-15 days
• Inflammatory cutaneous reaction leads to severe pruritic rash (papules/vesicles)
• Clinical manifestation leads to severe pruritis, dermatitis papules and vesicles with track-like cutaneous burrows interdigital flexural surfaces, palms; wrist, elbows, axillae, soles of feet, inguinal, genitalia
• Diagnosis is Microscopy (skin scraping-mite/eggs) to identify scabies and Norwegian scabies (in AIDS)
• Management is Permethrin
• Complications are secondary bacterial skin infection
• Prevention is treatment of infected individuals and sterilization of garments

Pediculosis (Human Lice Infestation)

• Etiology is Pediculosis humanus capitis (headlice); Pediculosis humanus humanus (body lice); Phthirus pubis (pubic lice)
• Epidemiology: Transmission occurs through prolonged interpersonal contact and fomites
• Lice are highly contagious and ubiquitous
• Head lice are typically found in retro-auricular and occipital scalp, laying eggs on hair shafts within 4-6mm of scalp
• Pubic lice ("crab lice") are found on pubic area skin with nits on pubic hair
• Clinical manifestations include pruritus, excoriated erythematous papules, regional lymphadenopathy, and nits on hair shafts
• Pediculosis ciliaris is an infestation of eyelid margins by Phthirus (pubic lice) and may result in conjunctivitis; ocular edema or corneal keratitis
• Diagnosis comes Visual detection (comb knits)/Microscopy for Pediculosis (Lice Infestation)
• First line treatment is Permethrin or Synergized Pyrethrins (Pyrthrin + Piperonyl butoxide
• Second-line treatment for refractory cases: Topical Benzyl Alcohol 5%; Spinosad 0.9%; Ivermectin 0.5%; Malathion 0.5%. Lindane is contraindicated because of neurotoxicity
• Complications are Impetigo (Staphylococcus aureus) or Acute post-streptococcal glomerulonephritis (APSGN)
• Prevention is treat infested person, avoid hair-hair contact, and avoid fomite spread (e.g. combs)

Trombidiosis ("Chiggers"; "Scrub Itch")

• Etiology: Trombicula autumnalis =mite ("harvest mite"), parasitic as larvae, but free-living as adults and nymphs
• Epidemiology: Appears late spring, early summer; Found in grassy areas (fields, gardens, lawns)
• Pathogenesis: Eggs of the mite are laid in soil under vegetation
• Mite larvae wait for vertebrate host to bite, reaching for thin areas of skin (ankles; axillae; groins/genital region)
• Larvae break skin with claws and inject cytolytic saliva (irritating) into the skin
• Clinical Manifestation: Within 24-48hrs of bites, macules develop into severely pruritic papules and vesicles
• It can spread diffusely on body, and pruritis can last about a week
• Diagnosis is clinical (H&P)
• Treatment: Self-limited disease; symptomatic treatment with zinc lotion; or steroid ointments, or oral antihistamines
• Prevention: Access to skin areas for mite to bite is stopped by tight-fitting clothing; insect repellents may prevent mite infestation

Chronic Granulomatous Dermatitis (Acanthamoebiasis)

• Etiology is Acanthamoeba culbertsoni (Protozoan; Amoeba)
• Primarily spreads Cutaneous acanthamoebiasis through skin wounds
• Affects Acanthamoeba Keratitis in US at 1:250,000 people, as well as contact lens wearers (1:10,000)
• Infection: cycle of cysts + trophozoites in infected fresh water or soil enter human via eyes, nose, or broken skin and migrate to blood, lungs, and CNS
• Skin manifestation is Acanthamoeba infection of intact epidermis with suppurative inflammation of subcutis, due to amoebic cysts and trophozoites
• Ocular inflammatory reaction affecting the cornea -> may lead to blindness (Acanthamoeba keratitis); seizures; confusion -> may lead to death (Granulomatous Amoebic Encephalitis)
• Diagnosis; Laboratory Tests: PCR; for Keratitis: culture of corneal scraping. For Encephalitis: CSF exam (spinal tap) + culture. Brain biopsy
• Specific Acanthamoeba dermatitis and Granulomatous Amoebic Encephalitis (GAE) must also be identified
• Treatment of Cutaneous acanthamoebiasis (CGD) is Fluorocytosine and Topical miltefosine
• Acanthamoeba Keratitis treated with topical cationic antiseptic agent such as Chlorhexidine (0.02%) with Brolene (0.1%) as well as keratoplasty
• Prevention occurs via avoiding freshwater exposure in endemic areas and avoid washing contact lens with tap water

Chagoma (Cutaneous Trypanosomiasis)

• Etiology is Trypanosoma cruzi, a flagellated protozoa
• Epidemiology: Latin America; 100,000 people are affected
• Acquired through bite of Reduviid bug (Triatoma), vertical transmission, and blood transfusion
• Transmits Trypomastigote (Trophozoite) to blood, and it transforms to amastigote in tissues (Heart; Skeletal muscles; Liver; Spleen; CNS)
• Virulence Factor: Antioxidant enzymes defend parasite against host oxidative assault, Host Response: Inflammation of organ systems (tissue reactions to amastigote)
• Clinical manifestation yields fever, lymphadenopathy, hepatosplenomegaly, Indurated inflammatory Subcutaneous lesion (Chagoma), Painless peri-orbital edema (Romana sign)
• Diagnosis: H&P; Microscopy (thick/thin blood smear - trypomastigote) + culture, PCR (blood), Skin Biopsy
• Management is Benznidazole and Nifurtimox
• Complications include secondary infection (cellulitis; bacteremia)
• Prevention is use of insecticide and insect repellent, housing eliminate breeding areas of reduviid bug

Enterobius Dermatitis (Pin Worm Dermatitis)

• Etiology: Enterobius vermicularis Intetsinal Nematode, aka "Pin worm"
• Epidemiology: Common in children
• Female pinworms leave the intestinal tract while the infected person sleeps and lay eggs on the skin around the anus
• Eggs asticky, jelly-like substance that, along with the movements of the female pinworm, causes severe pruritis; autoinoculation occurs with children scratching their perianal area and poor sanitation
• Clinical Manifestations: Perianal irritation/erythema, perianal pruritis; asymptomatic (30%)
• Diagnosis Microscopy (Eggs -> Scotch Tape Test); Stool O&P
• Management: Pyrantel pamoate (OTC) Drug of Choice; Albendazole, Mebendazole
• Complications are secondary bacterial skin infection
• Prevention is good hygiene in children, wash bed linen, and treat infected

Larva Currens

• Etiology: Strogyloides stercoralis
• Epidemiology:: Worldwide transmission via worldwide, Definitive Host=Human; Dog; Filariform larvae (infective form) penetrate intact human Skin or are ingested
• Filariform larvae invade intact skin, rapidly burrows subcutaneously (“Larva currens")
• Proteases facilitate penetration of skin by worm. -> Filariform enter blood -> Larvae migrate to Lungs -> coughed up and swallowed -> enter Intestines-> form Adult - Rhabiditiform Larvae (non-infective form) excreted in stool
• Clinical Manifestations: Asymptomatic with intensely pruritic “rapidly migrating" (5-15cm/hr) erythematous rash, linear serpiginous-appearing, often found subcutaneously on gluteal area, perineum and thighs; coughing or diarrhea
• Diagnosis: Stool for ova & Parasites/Microscopy. PCR. Eosinophilia, strongyloidiasis, Larva currens; Loeffler syndrome(Benign Transient Pulmonary Eosinophilia)
• Management: Ivermectin
• Complications: Secondary bacterial skin infections
• Prevention: Sanitation

Sea Lice Eruption (Sea bathers eruption)

• Sea lice are Linuche unguiculata (thimble jelly fish larvae), sea lice=Copepod crustacean
• Epidemiology: Sea lice are jellyfish larvae that get trapped in swimmers' bathing suits, where they sting and cause a pruritic rash
• Parasitic copepod (tiny crustaceans) that attach to fish (e.g. salmon) are also called sea lice
• The bite/sting manifests as a prickly or mild stinging sensation while in sea water; may start from a few minutes to hours after leaving the water
• Clinical Manifestation: Intensely pruritic erythematous papules, can cause nausea, vomiting, diarrhea; pruritis is worse at night and disturbs sleep; may last for 2-14 days
• Clinical diagnosis in those with sea bather's eruption
• Management: Symptomatic through dilute vinegar or alcohol to irritated areas and applying cloth-covered ice packs, as well as non-steroidal inflammatory agents
• Complications are secondary bacterial infection from scratching
• Prevention: Avoid ocean swimming

Dracunculiasis (Guinea Worm Infestation)

• Etiology is Dracunculus medinensis, nematode aka "Guinea worm" in Africa
• Epidemiology: Transmission through oral ingestion of contaminated freshwater crustaceans (Cyclops) containing Dracunculus larvae
• Ingested cyclops are killed by gastric juice, but Dracunculus larvae survive; transform into adult worms, which enter the small intestine, penetrate the mucosa of the duodenum-> invade retroperitoneal and subcutaneous connective tissue via Lymphatics
• Exits via Skin surface, larvae released into fresh water when exposed
• Adult female worm secretes a toxin that causes blisters on skin (typically feet/ankle), and discharge milky-white fluid containing larvae, causing an allergic reaction
• Clinical manifestations: rash involving a painful erythematous pruritic blister/ulcer on skin, usually of lower extremity which contains an adult worm that extrudes through skin surface on feet, ankle, leg, or back
• Intense pruritis at site of extrusion, nausea. vomiting, and urticaria may occur
• Affected leg in water facilitating twirling extruding worm on stick facilitates extrusion
• X-ray may show calcified worm in tissue after worm dies
• Diagnosis occurs through ELISA or IFA
• Management: Antihistamine, steroids, Metronidazole, Niridazole, or Thiabendazole
• Complications:: Ulcers by worm lead to secondary bacterial infections
• Prevention: Avoid wading in contaminated water

Calabar Swelling (Loiasis)

• Etiology: Loa Loa, filarial nematode, aka "Africa Eye Worm" transmitted via the bite from Mango fly (Chrysops) carrying larvae
• Endemic to West and Central Africa
• Larvae migrate into skin/subcutaneous tissue (resulting in inflammatory edema of skin, near and distant to bite site)=Calabar swelling larvae also migrate to eye (subconjunctiva) via blood
• Clinical Manifestation: Calabar swellings= localized, non-tender swellings usually found on the arms and legs and near joints; pruritus (generalized or localized to area of swelling)
• Presents Calabar swelling of eye
• Diagnosis: Microscopy (blood) microfilariae; PCR; Subconjunctival biopsy
• Management: Ivermectin
• Prevention: Vector control and wearing protective clothing

Myiasis (Fly larvae Infestation)

• Etiology; Dermatobia hominis (Human Bot Fly) Larvae
• Epidemiology; Mainly in the tropics or sub-tropics
• Myiasis presents in several forms: furuncular, wound and migratory
• Pathogenesis: Skin infestation of humans with the Larvae ("Maggots") of the Diptera order of fly species
• Fly deposit their eggs on or near a wound or sore or on a blood-sucking vector (mosquito) which leads to larvae that burrow into the skin hatching
• Clinical Manifestation: Furuncular Myiasis presents as a nodule with a central respiratory pore, and symptoms of formication, pruritus sharp pain and discharge
• Diagnosis happens through H&P, Finding of fly larvae in tissue
• Surgical removal of larvae; larvae may emerge from skin to treat Myiasis
• Complications; Impetigo, Cellulitis, Skin necrosis, Tetanus
• Prevention; Proper hygiene and mosquito avoidance

Dirofilariasis

• Etiology; Dirofilaria immitis
• Epidemiology; Transmitted via Mosquito bite (Aedes, Culex, Anopheles, Mansoni) ; transmits larvae with bite of human after acquiring it from bite of dog (natural host)
• Most commonly causes pulmonary disease; adults can live for 5-10 years
• Pathogenesis; When mosquito bites adult worm enters subcutaneous area -> skin nodules and/or subconjunctiva and release microfilaria into blood; Larvae may become encapsulated in infarcted lung tissue and produce well-defined pulmonary nodules and rarely larvae form nodules in the eyes, brain, and/or testes Clinical Manifestation; Mostly pulmonary disease with cough, hemoptysis, chest pain, fever, and pleural effusion Diagnosis; biopsy of skin nodule/ chest X-ray Dirofilariasis must be identified Surgical removal of skin granuloma or large pulmonary granulomas is indicated as well as avoiding mosquitoes and using insect repellants for management Complications could include pulmonary infarction (often the indicator of the infection)

Cases/ Diagnoses

• Case #1: Localized non-tender pruritic inflammatory edema on arms/legs/joints, near bite of a mango fly transmitted by a filarial nematode that often settles in subconjunctiva and is endemic to West and Central Africa indicates Calabar Swelling (Loiasis)
• Case #2: Perianal pruritic erythema with infestation of eggs and or female pin worms (tiny intestinal nematode), common in children, autoinoculation and tested with a scotch-tape test indicative of Enterobius Dermatitis
• Case #3: Highly pruritic and excoriated erythematous papules on scalp or pubis, with nits or lice on hair strand, regional lymphadenopathy, infests hair + scalp/pubis, highly contagious and treated with permethrin/pyrethrin with complications of impetigo & APSGN are indicative of Pediculosis
• Case #4: Severely pruritic serpiginous rash, typically on lower extremities from filariform larvae (nematode from dogs/cats) & tunnel) grows slowly (1-2cm per day) through epidermis; Exposure to parks frequented by dogs/cats (feces) and can be treated with albendazole for Cutaneous Larva Migrans (Ancylostomiasis)
• Case #5: Hypopigmented macules form painless papules that form diffuse nodular lesions and become ulcerated indicative of that Mimics Leprosy that is typically on face and extremities as well as Flagellated protozoan: Promastigote (enters skin) to Amastigote (in macrophages, RES); Transmitted by bite of Sandfly (Phlebotomus) and preceded by Kala azar. (Intermittent high fever, malaise, anorexia, night sweats, diarrhea, hepatosplenomegaly, lymphadenopathy).Dx: Montenegro test and treat TX= Pentavalent antimonials for Dermal Leishmaniasis
• Case #6: Severely pruritic papulo-vesicular rash with track-like cutaneous burrows interdigitalflexural/palmar/wrists/elbowaxillae/soles of feet/inguinal/genital areas, transmitted by mite (eggs deposited in burrows):; commonly in infants and children; immunocompromised, highly contagious= Scabies
• Case #7: Suppurative inflammation of subcutis of skin with intact nodular epidermis (associated with amoebic cysts and trophozoites).Exposure to freshwater/soil contaminated with amoebae; enters skin wound/ulcers, Infective agent= amoebic protozoan Common with immunocompromised host and causes keratitits(in contact lenses and GAE= Cutaneous Amoebiasis (Acanthamoebiasis)
• Case #8::Intensely pruritic rapidly migrating (5-15cm/hr) erythematous burrow, “serpiginous track" often around gluteal, thighs and perineum, Rash is secondary to subcutaneous burrows of filariform larvae of nematode=infective agent that Nematode also infects Lungs and intestines and humans get infected when filariform larvae (penetrate intact human and can cause benign Transient Pulmonary eosinophilia= Larva Currens (Strongyloidiasis))
• Case # 9:Intensely pruritic erythematous papules (often under swimwear that is worse at nightdisturbs sleep, lasts 2-14 day while infective agent= jellyfish larvae that get trapped in bathing suit in ocean is treated with dilute vinegar/alcohol and can cause nausea, vomiting, diarrhea = Sea Bathers Eruption (Sea Lice)
• Case #10: Pruritic rash manifesting with hypopigmented patches, often on lower extremities as Secondary to subcutaneous infestation of filarial nematode that gets transmitted through bite of Black Fly (Simulium damnosum) and Commonly seen in West Africa = Onchocercoma (Onchocerciasis)
• Case #11: Diffuse pruritic papular eruption typically on extremities known as Swimmer's Itch" as history of Katayama fever (fever, cough, bronchospasm, lymphadenopathy, eosinophilia, hepatosplenomegaly and exposed to cercaria of blood fluke when wading in water infested by Snails= Cercarial dermatitis (Schistosomiasis))
• Case #12; Rash manifests through painful pruritic erythematous blister/ulcer on skin (usually feet/ankle/lower extremity/back) with extrusion of thread-like adult female filarial nematode worm (in milky secretion)/ affected in leg water facilitating twirling extruding worm on stick facilitates extrusion as X-ray shows calcification of worm in tissue with 2ndary bacterial infection that is mainly seen in Africa = Dracunculiasis (Guinea Worm)
• Case #13:Painful and pruritic skin nodule/furuncle with a central respiratory pore and pustular discharge with a fly larvae ("maggots") carried to skin by blood-sucking mosquito which shows symptoms of formication = Myasis
• Case #14: Single firm, moveable painful subcutaneous nodule that migrates under skin causing erythema and edema (especially on upper body and eye) as infective agent by tiny filarial nematode by mosquito bite (Aedes, Culex, Anopheles, Manosni) from dog & also causes subconjunctival or pulmonary nodules = Subcutaneous difilariasis
• Case #15: Diffuse pruritic skin eruption (macule-papule vesicle affect ankle, axillae and groin genital area as secondary to bit of harvest mit larvae in late spring/summer in grassy areas= trombidiosis(chiggers)
• Case # 16: Indurated inflammatory subcutaneous lesion with fever; lymphadenopathy, hepatosplenomegaly, infective agent: flagellated protozoan; Transmission of Trypomastigote in blood via bite of Reduviid bug Amastigote with painless periorbital Edema= Chagoma (S. American Trypanosomiasis)