History

Fact Explanation
Slowly progressive poor healing ulcer at mucucutaneous junctions Leishmaniasis is transmitted by the bite of female phlebotomine sandflies. The sandflies inject the infective stage, promastigotes, during blood meals Promastigotes that reach the puncture wound are phagocytized by macrophages and transform into amastigotes Amastigotes multiply in infected cells and affect different tissues, depending in part on the Leishmania species This originates the clinical manifestations of leishmaniasis. Sandflies become infected during blood meals on an infected host when they ingest macrophages infected with amastigotes and In the midgut, the parasites differentiate into promastigotes which multiply and migrate to the proboscis.[8] The parasites invade the the mucocutaneous areas and produce a inflammatory reaction. [1]
Difficulty in swallowing Due to inflammatory ulcers in oral cavity,palate,larynx. [5]
Respiratory disturbance, voice change Destructive lesions of palate,nasal septa cause oedema and narrowing the airways. [3,5]
Nasal congestion, nasal bleeding Inflammatory lesions at nose cause oedema and damage vessels causing bleeding and congestion. [5]
Risk people - immunocompromised people such as patients with AIDS Due to low immune response against the infection. [2]
Travel history to endemic areas L. tropica,L. major are the main causative parasites.The disease is endemic throughout parts of Africa, India, the Middle East, southern Europe, and Central and South America, habitats that provide stable temperatures, high humidity and decaying organic matter. [4,6,7]
Inadequate treatments of previous leishmaniasis episodes if the treatments inadequate or neglected the disease can relapse and reappear. [9]
References
  1. GAWKRODGER, D.J,Infections.GAWKRODGER, D.J. Dermatology, an illustrated colour text. 3rd ed. China: Elsevier, 2002,pp.57
  2. ALI A. Leishmaniases and HIV/AIDS co-infections: review of common features and management experiences. Ethiop Med J [online] 2002 Apr:37-49 [viewed 04 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12802830
  3. AMATO VS, TUON FF, SIQUEIRA AM, NICODEMO AC, NETO VA. Treatment of mucosal leishmaniasis in Latin America: systematic review. Am J Trop Med Hyg [online] 2007 Aug, 77(2):266-74 [viewed 12 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/17690398
  4. HANDMAN E.. Leishmaniasis: Current Status of Vaccine Development. Clinical Microbiology Reviews [online] 2001 April, 14(2):229-243 [viewed 12 June 2014] Available from: doi:10.1128/CMR.14.2.229-243.2001
  5. STRAZZULLA ALESSIO, COCUZZA SALVATORE, PINZONE MARILIA RITA, POSTORINO MARIA CONCETTA, COSENTINO STEFANO, SERRA AGOSTINO, CACOPARDO BRUNO, NUNNARI GIUSEPPE. Mucosal Leishmaniasis: An Underestimated Presentation of a Neglected Disease. BioMed Research International [online] 2013 December, 2013:1-7 [viewed 12 June 2014] Available from: doi:10.1155/2013/805108
  6. MONCAZ AVIAD, FAIMAN ROY, KIRSTEIN OSCAR, WARBURG ALON, KAMHAWI SHADEN. Breeding Sites of Phlebotomus sergenti, the Sand Fly Vector of Cutaneous Leishmaniasis in the Judean Desert. PLoS Negl Trop Dis [online] 2012 July [viewed 14 June 2014] Available from: doi:10.1371/journal.pntd.0001725
  7. PALUMBO EMILIO. Treatment strategies for mucocutaneous leishmaniasis. J Global Infect Dis [online] 2010 December [viewed 14 June 2014] Available from: doi:10.4103/0974-777X.62879
  8. HAILU ASRAT, MUDAWI MUSA AHMED, ROYCE CATHERINE, WASUNNA MONIQUE. Visceral Leishmaniasis: New Health Tools Are Needed. Plos Med [online] 2005 December [viewed 14 June 2014] Available from: doi:10.1371/journal.pmed.0020211
  9. REVEIZ LUDOVIC, MAIA-ELKHOURY ANA NILCE SILVEIRA, NICHOLLS RUBéN SANTIAGO, SIERRA ROMERO GUSTAVO ADOLFO, YADON ZAIDA E., SCHALLIG HENK D. F. H.. Interventions for American Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review Update. PLoS ONE [online] 2013 April [viewed 20 June 2014] Available from: doi:10.1371/journal.pone.0061843

Examination

Fact Explanation
Destructive ,nodular mucocutaneous lesions- In nasal septum, lips, oral cavity,palate,larynx,tongue Due to the ongoing inflammatory process [1,2] The sandflies inject the infective stage, promastigotes, during blood meals Promastigotes that reach the puncture wound are phagocytized by macrophages and transform into amastigotes Amastigotes multiply in infected cells and affect different tissues, depending in part on the Leishmania species This originates the clinical manifestations of leishmaniasis, mostly the primary site of the lesion is skin and some species can metastasis to mucosal surfaces and induce inflammation. [3,5]
Dyspnoea Dyspnoea means difficulty in breathing this is due to destructive lesions in the upper respiratory tract mainly nose,palate,larynx.As respiratory tract gets inflamed and edematous the air waya get narrowed and breathing difficulties occur. [2]
Dysphonia Dysphonia means difficulty in voice production this is due to lesions involving larynx. As sound production is from the larynx this occur. [2]
Nasal bleeding Due to lesions in the associated areas of nose cause damage to blood vessels and bleeding occur.[4]
References
  1. MURPHY, M.F., J.S. WAINSCOAT, K.J. PASI. Protozoal infections. ed. KUMAR, Parveen and Michal CLARK. KUMAR & CLARK Clinical Medicine. 8th ed. Spain: Elsevier Ltd,2012, pp. 149
  2. STRAZZULLA ALESSIO, COCUZZA SALVATORE, PINZONE MARILIA RITA, POSTORINO MARIA CONCETTA, COSENTINO STEFANO, SERRA AGOSTINO, CACOPARDO BRUNO, NUNNARI GIUSEPPE. Mucosal Leishmaniasis: An Underestimated Presentation of a Neglected Disease. BioMed Research International [online] 2013 December, 2013:1-7 [viewed 12 June 2014] Available from: doi:10.1155/2013/805108
  3. HAILU ASRAT, MUDAWI MUSA AHMED, ROYCE CATHERINE, WASUNNA MONIQUE. Visceral Leishmaniasis: New Health Tools Are Needed. Plos Med [online] 2005 December [viewed 14 June 2014] Available from: doi:10.1371/journal.pmed.0020211
  4. STRAZZULLA ALESSIO, COCUZZA SALVATORE, PINZONE MARILIA RITA, POSTORINO MARIA CONCETTA, COSENTINO STEFANO, SERRA AGOSTINO, CACOPARDO BRUNO, NUNNARI GIUSEPPE. Mucosal Leishmaniasis: An Underestimated Presentation of a Neglected Disease. BioMed Research International [online] 2013 December, 2013:1-7 [viewed 12 June 2014] Available from: doi:10.1155/2013/805108
  5. REVEIZ LUDOVIC, MAIA-ELKHOURY ANA NILCE SILVEIRA, NICHOLLS RUBéN SANTIAGO, SIERRA ROMERO GUSTAVO ADOLFO, YADON ZAIDA E., SCHALLIG HENK D. F. H.. Interventions for American Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review Update. PLoS ONE [online] 2013 April [viewed 20 June 2014] Available from: doi:10.1371/journal.pone.0061843

Differential Diagnoses

Fact Explanation
Syphilis it produce inflammatory lesions in mucous membranes, demonstration of organisms by dark field examination,serological tests of fluid from the base of the lesion to differentiate. As syphilis is a sexually transmitted disease the contact history is also important. (not in leishmaniasis) [1,2,3]
Yaws Produces ulcerated papilloma in skin. A diagnosis of primary yaws was established by clinicians on the basis of chronic (> 2 weeks), painless, atraumatic ulcers with raised margins. Criteria for the diagnosis of secondary yaws included one of the following: multiple hyperkeratotic papules, polyarthralgia, bone pain and swelling affecting the fingers or toes, forearms, and tibia or fibula, serological tests use to confirm. [1,3,4]
Leprosy Produces multiple macular,papular,nodular plaque like lesions,usually painful and there is a nerve involvement(reduce sensation,reduce sweating) not as leishmaniasis.confirm by histologically using biopsy. [4,5,6]
Blastomycosis The cutaneous manifestations of blastomycosis come in two forms, verrucous and ulcerative.Verrucous skin lesions, which lie above subcutaneous abscesses(not in leishmaniasis), are raised and crusted with an irregular shape and sharp borders. Histologically, there is papillomatosis with downward proliferation of the epidermis and formation of microabscesses to confirm look for yeast forms in biopsy specimens with a special stain, such as Grocott-Gomori methenamine silver nitrate (GMS). [1,6,7,8]
References
  1. CARLSON J ANDREW, DABIRI GANARY, CRIBIER BERNARD, SELL STEWART. The Immunopathobiology of Syphilis: The Manifestations and Course of Syphilis Are Determined by the Level of Delayed-Type Hypersensitivity. The American Journal of Dermatopathology [online] 2011 July, 33(5):433-460 [viewed 14 June 2014] Available from: doi:10.1097/DAD.0b013e3181e8b587
  2. MITJÃ ORIOL, Å MAJS DAVID, BASSAT QUIQUE, SMALL PAMELA L. C.. Advances in the Diagnosis of Endemic Treponematoses: Yaws, Bejel, and Pinta. PLoS Negl Trop Dis [online] 2013 October [viewed 14 June 2014] Available from: doi:10.1371/journal.pntd.0002283
  3. LOCKWOOD DIANA N. J., NICHOLLS PETER, SMITH W. CAIRNS S., DAS LORETTA, BARKATAKI PRAMILA, VAN BRAKEL WIM, SUNEETHA SUJAI, VINETZ JOSEPH M.. Comparing the Clinical and Histological Diagnosis of Leprosy and Leprosy Reactions in the INFIR Cohort of Indian Patients with Multibacillary Leprosy. PLoS Negl Trop Dis [online] 2012 June [viewed 14 June 2014] Available from: doi:10.1371/journal.pntd.0001702
  4. SACCENTE M., WOODS G. L.. Clinical and Laboratory Update on Blastomycosis. Clinical Microbiology Reviews [online] December, 23(2):367-381 [viewed 14 June 2014] Available from: doi:10.1128/CMR.00056-09
  5. CARLSON JA, DABIRI G, CRIBIER B, SELL S. THE IMMUNOPATHOBIOLOGY OF SYPHILIS: THE MANIFESTATIONS AND COURSE OF SYPHILIS ARE DETERMINED BY THE LEVEL OF DELAYED-TYPE HYPERSENSITIVITY Am J Dermatopathol [online] 2011 Jul, 33(5):433-460 [viewed 21 June 2014] Available from: doi:10.1097/DAD.0b013e3181e8b587
  6. MITJA O., HAYS R., LELNGEI F., LABAN N., IPAI A., PAKARUI S., BASSAT Q.. Challenges in Recognition and Diagnosis of Yaws in Children in Papua New Guinea. American Journal of Tropical Medicine and Hygiene [online] December, 85(1):113-116 [viewed 21 June 2014] Available from: doi:10.4269/ajtmh.2011.11-0062
  7. LOCKWOOD DN, NICHOLLS P, SMITH WC, DAS L, BARKATAKI P, VAN BRAKEL W, SUNEETHA S. Comparing the Clinical and Histological Diagnosis of Leprosy and Leprosy Reactions in the INFIR Cohort of Indian Patients with Multibacillary Leprosy PLoS Negl Trop Dis [online] , 6(6):e1702 [viewed 21 June 2014] Available from: doi:10.1371/journal.pntd.0001702
  8. SACCENTE M, WOODS GL. Clinical and Laboratory Update on Blastomycosis Clin Microbiol Rev [online] 2010 Apr, 23(2):367-381 [viewed 21 June 2014] Available from: doi:10.1128/CMR.00056-09

Investigations - for Diagnosis

Fact Explanation
Punch biopsy Demonstrate organisms by tissue staining procedures.After collection of the cytology brush specimens and cleansing the lesion again with isopropyl alcohol, mucosal lesions were anesthetized with 20 mg/mL lidocaine spray. Two small biopsy specimens were then obtained from lesions using sterile nasal or ethmoid biopsy forceps. The tissue was placed in 10% formalin for histopathology with hematoxylin and eosin, Ziehl-Neelsen, and Giemsa staining. Sterile gauze was applied with pressure to the mucosal lesion until hemostasis was achieved. [1,2,5,6]
Polymerase chain reaction[PCR] Demonstrate the parasites DNA.So this is very accurate investigation. Prior to DNA extraction, samples(tissue biopsy) were centrifuged at 3000 g for 5 min and ethanol was discarded. Biopsied tissues were disaggregated with a sterile scalpel. Disaggregated tissue and cytology brushes were processed for DNA isolation using the High Pure PCR Template Preparation Kit. [1,2,6]
Leishmanin skin test Demonstrate the delayed type( cell mediated) hypersensitivity reaction people who are infected.Previously infected people have antibodies against parasites and they act with injected antigens and form localized induration with redness.A positive result was indicated by ≥5 mm of erythema and induration [2,3,5,6]
Tissue culture and staining To demonstrate the parasite forms (amastigote) by using special stains such as Giemsa. [4,5,6]
References
  1. MURPHY, M.F., J.S. WAINSCOAT, K.J. PASI. Protozoal infections. ed. KUMAR, Parveen and Michal CLARK. KUMAR & CLARK Clinical Medicine. 8th ed. Spain: Elsevier Ltd,2012, pp. 149
  2. SOUTHWOOD TR, KHALAF S, SINDEN RE. The micro-organisms of tsetse flies. Acta Trop [online] 1975, 32(3):259-66 [viewed 12 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/1986
  3. SADEGHIAN GITI, ZIAEI HENGAMEH, BIDABADI LEILASHIRANI, NILFOROUSHZADEH MOHAMMADALI. Evaluation of leishmanin skin test reaction in different variants of cutaneous leishmaniasis. Indian J Dermatol [online] 2013 December [viewed 12 June 2014] Available from: doi:10.4103/0019-5154.110838
  4. STRAZZULLA ALESSIO, COCUZZA SALVATORE, PINZONE MARILIA RITA, POSTORINO MARIA CONCETTA, COSENTINO STEFANO, SERRA AGOSTINO, CACOPARDO BRUNO, NUNNARI GIUSEPPE. Mucosal Leishmaniasis: An Underestimated Presentation of a Neglected Disease. BioMed Research International [online] 2013 December, 2013:1-7 [viewed 12 June 2014] Available from: doi:10.1155/2013/805108
  5. REVEIZ LUDOVIC, MAIA-ELKHOURY ANA NILCE SILVEIRA, NICHOLLS RUBéN SANTIAGO, SIERRA ROMERO GUSTAVO ADOLFO, YADON ZAIDA E., SCHALLIG HENK D. F. H.. Interventions for American Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review Update. PLoS ONE [online] 2013 April [viewed 20 June 2014] Available from: doi:10.1371/journal.pone.0061843
  6. BOGGILD ANDREA K., VALENCIA BRAULIO MARK, VELAND NICOLAS, PILAR RAMOS ANA, CALDERON FLOR, AREVALO JORGE, LOW DONALD E., LLANOS-CUENTAS ALEJANDRO, EL-SAYED NAJIB M.. Non-Invasive Cytology Brush PCR Diagnostic Testing in Mucosal Leishmaniasis: Superior Performance to Conventional Biopsy with Histopathology. PLoS ONE [online] 2011 October [viewed 20 June 2014] Available from: doi:10.1371/journal.pone.0026395

Management - General Measures

Fact Explanation
Vector control- use insecticides [pyrethroids], reduces the breeding places Spraying insecticides in houses to kill the sand flies. Most insecticides are organophosphates and carbamates. Acetylcholinesterase (AChE) is a common target for carbamates and organophosphates. These insecticides diffuse ti insect and blocks transmission of nerve impulses by irreversible inhibition of AChE at cholinergic synapses, causing insect death. As leishmaniasis carries by the sand flies by control sand flies can reduce the morbidity. [1,2,5]
Use bed nets as personal protection [pyrethroid-impregnated nets] As the disease is carried by sand fly with the reduction of sand fly bites and by the killing the transmission can be limited. [1,2,5]
Use repellents as personal protection To prevent an arthropod from entering a space occupied by a potential human host to reduce encounters between humans and vectors thereby eliminating or reducing the probability (risk) of pathogen transmission. [4]
Treated infected people Vectors bite infected people and transmit the disease. [3]
Advice for travelers- Use bed nets,insectisides, those who are travel to endemic areas(previously mention) Reduces the sand fly bites. [2]
References
  1. MURPHY, M.F., J.S. WAINSCOAT, K.J. PASI. Protozoal infections. ed. KUMAR, Parveen and Michal CLARK. KUMAR & CLARK Clinical Medicine. 8th ed. Spain: Elsevier Ltd,2012, pp. 149
  2. ROBERTS M. T. M.. Current understandings on the immunology of leishmaniasis and recent developments in prevention and treatment. British Medical Bulletin [online] 2006 February, 75-76(1):115-130 [viewed 12 June 2014] Available from: doi:10.1093/bmb/ldl003
  3. PISCOPO T. V, MALLIA AZZOPARDI C.. Leishmaniasis. Postgraduate Medical Journal [online] 2007 February, 83(976):649-657 [viewed 14 June 2014] Available from: doi:10.1136/pgmj.2006.047340corr1
  4. ACHEE NICOLE L, BANGS MICHAEL J, FARLOW ROBERT, KILLEEN GERRY F, LINDSAY STEVE, LOGAN JAMES G, MOORE SARAH J, ROWLAND MARK, SWEENEY KEVIN, TORR STEVE J, ZWIEBEL LAURENCE J, GRIECO JOHN P. Spatial repellents: from discovery and development to evidence-based validation. Array [online] 2012 December [viewed 21 June 2014] Available from: doi:10.1186/1475-2875-11-164
  5. AHOUA ALOU LUDOVIC P, KOFFI ALPHONSINE A, ADJA MAURICE A, TIA EMMANUEL, KOUASSI PHILIPPE K, KONé MOUSSA, CHANDRE FABRICE. Distribution of ace-1R and resistance to carbamates and organophosphates in Anopheles gambiae s.s. populations from Côte d'Ivoire. Array [online] 2010 December [viewed 21 June 2014] Available from: doi:10.1186/1475-2875-9-167

Management - Specific Treatments

Fact Explanation
Systemic-Pentavalent antimony salts(gold standerd treatment) eg: sodium stibogluconate and meglumine antimoniate This causes activation of patient immune system by inducing cytokine in order to kill the protozoa.The pentavalent antimonials are considered the gold standard for treatment of leishmaniasis. Two preparations are currently available abroad: sodium stibogluconate for intravenous and intramuscular administration and meglumine antimoniate for intramuscular administration. The biochemical basis for their effectiveness is unknown, but may involve inhibition of ATP synthesis. The drugs exist only in parenteral forms. The dosage is usually given in Sb equivalents (mg/kg/day). [1,2,4]
Systemic-Amphotericin B It has antifungal activity and evidence proves it also helps to kill the protozoa. [1,2]
Local-Intralesional therapy with Pentavalent antimony salts in order to kill the protozoa by inducing inflammatory reactions. This means carefully infiltrating the area around the lesion, including the base of the lesion. A fine gauge (25G) needle is used to inject the drug under pressure as the needle advances. Injection into the dermis is difficult, as the tissue space is small. The drug must not be injected into the subcutaneous tissue, where it is rapidly absorbed and does not reach the site of infection.[2,3,4]
Local-Surgical excision In order to remove the inflammatory tissue. [5]
Local-cryotherapy,cauterization. Protozoa very sensitive to heat so these help to kill the heat sensitive protozoa. Cryotherapy is the most common and it is performed by repeated topical applications of liquid nitrogen with a cotton-tipped applicator or a cotton swab with moderate pressure to the lesion, up to 2 mm outside the lesion margin. The freezing time per application is 15-20 second. The procedure is repeated two or three times at short intervals, resulting in a total time of 30-120 second. Adequate application is reflected in the whitening of the skin at 2-3 mm outside the margins of the lesion. [5]
References
  1. PALUMBO EMILIO. Treatment strategies for mucocutaneous leishmaniasis. J Global Infect Dis [online] 2010 December [viewed 04 June 2014] Available from: doi:10.4103/0974-777X.62879
  2. ESFANDIARPOUR IRAJ, FARAJZADEH SAEEDEH, RAHNAMA ZAHRA, FATHABADI ELAHE ARABPOOR, HESHMATKHAH AMIREH. Adverse effects of intralesional meglumine antimoniate and its influence on clinical laboratory parameters in the treatment of cutaneous leishmaniasis. [online] December, 51(10):1221-1225 [viewed 13 June 2014] Available from: doi:10.1111/j.1365-4632.2012.05460.x
  3. KOCYIGIT A, GUR S, GUREL MS, BULUT V, ULUKANLIGIL M. Antimonial therapy induces circulating proinflammatory cytokines in patients with cutaneous leishmaniasis. Infect Immun [online] 2002 Dec, 70(12):6589-91 [viewed 13 June 2014] Available from: http://www.ncbi.nlm.nih.gov/pubmed/12438329
  4. PISCOPO T. V, MALLIA AZZOPARDI C.. Leishmaniasis. Postgraduate Medical Journal [online] 2007 February, 83(976):649-657 [viewed 14 June 2014] Available from: doi:10.1136/pgmj.2006.047340corr1
  5. PALUMBO EMILIO. Treatment strategies for mucocutaneous leishmaniasis. J Global Infect Dis [online] 2010 December [viewed 14 June 2014] Available from: doi:10.4103/0974-777X.62879