هوالشافی

1. هوالشافی Case presentation By : Dr, H. Mozayyeni Jan 2018

2. CC , PI CC : Two huge tumoral and cauliflowerr-like lesions on Rt elbow PI: A 45-year-old Iranian man with renal transplant and with two tumoral lesions was admitted to our dermatology clinic on Jun 2017 . The patient was suffering from chronic renal failure due to diabetes (non-insulin-dependent diabetes mellitus, NIDDM) for several years before this admission. He presented to us with two huge tumoral and indurated plaque on elbow.

4. Cont’d • The patient had no systemic symptom and sign at first visit , such as • Fever • Weight loss • Lymphadenopathy • Cough • Hepatosplenomegally

5. PMH , DH • Due to chronic renal failure, renal transplantation was performed on the patient in August 2010. After transplantation, he received cyclosporine 7.5 mg/kg daily .

6. Lab data • Skin smear and histopathology of skin showed leishman bodies and confirmed the diagnosis. • Histopathology : • Skin tissue is seen with orthokeratosis, acanthosis, spongiosisand epidermal ulceration . Dermis show many leishman bodies in histiocytesand perivascular mononuclear cell infiltration .

8. Other lab test • CBC Diff WBC:9.6 RBC:4.2 , Hb :11.7 PLT :298 • ESR : 5 , CRP : negative • RFT Bun :113 Cr : 2.9 • LFT SGOT :15 SGPT :24 ALK-P : 192 Bill D : 0.3 Bill T : 0.8 • Abdomen and pelvic ultrasonography is normal

9. Treatment • Due to • Immunosuppression state • History of renal transplantation • Increase of creatin niosomalparomomycin cream ( Topical BD ) , Cryotherapy ( every three weeks once ) was started for patient . Three month after starting treatment , not only the response was not seen , but the lesions gradually be came larger .

10. Failure of treatment • Second choice Intraleisonalglucantim ( weekly) + Cryotherapy ( every two weeks once) Outcome Intraleisionalglucantim and cryotherapy were unsuccessful and patient developed new lesions . Physical examination showed multiple papules on erythematous surface with central umbilication on the face and upper exteremity.

12. LEISHMANIASIS • Chronic parasitic (protozoan) disease in which organisms are found within phagolysosomes of mononuclear phagocytes • The vector is a sandflyinfected with promastigotes • Reservoirs : Human , dog , foxes , rodent , • The most common cutaneous finding is a papule that develops at the site of inoculation and then enlarges and ulcerates

13. Epidemiology • Worldwide, there are approximately 2 million new cases of leishmaniasisannually, with cutaneous or mucocutaneous disease in >75% , of affected individuals, and it is estimated that 12 million people are currently infected • Old World cutaneous leishmaniasisis usually due to L. major or L. tropica, and less often to L. infantum(Europe) or L. aethiopica. • In the New World, cutaneous leishmaniasisis caused primarily by subspecies of L. mexicana and mucocutaneous disease is associated with L. braziliensis. • Infections with L. donovani, L. infantum(especially in the setting of HIV infection) and L. chagasiare the major causes of visceral leishmaniasis

14. Classification • There is an old classification that divides leishmaniosis to : • Cutaneous , • Diffuse cutaneous , • Muco-cutaneous • Visceral leishmaniasis ( Kala- azar)

15. New Classification of Leishmaniosis • Localized cutaneous leishmaniasis • Diffuse cutaneous leishmaniasis • Mucosal leishmaniasis • Visceral leishmaniasis • Disseminated (skin & visceral) leishmaniasis

16. Types of cutaneous leishmaniasis • ACL , urban type , dry (acute) • ZCL , rural type , wet (acute) • Multiple bite (acute) • Ide reaction (acute) • Diffuse (chronic) • Disseminated (chronic) • Recidivance or lupoid (chronic) • Abortive (chronic /acute)

17. Multiple lesions • Multiple bite ( acute / chronic) • Ide reaction (acute) • Diffuse cutaneous leishmaniasis (chronic) • Disseminated cutaneous & systemic leishmaniasis (acute)

18. Diffuse cutaneous leishmaniasis • Non ulcerated lesions starting mosltly on face , then spread to trunk & extremities • Caused by L. athiopica, L. tropica , L. braziliansis • Very resistant to first line of treatments • Looks like leprosy , some accompanied by AIDS • Has tendency to chronicity • Composed of hard ,flesh colored non ulcerated indurated nodules & plaques mostly in the skin of facial area , trunk & extremities

19. Disseminated cutaneous leishmaniasis • Occurs in CMI anergy states • Occurs in immune deficiencies , AIDS, Malignancies ,chemotherapy, corticosteroids therapy • Systemic involvement may coexist • Can be lethal • Some use the word “ Diffuse “ for this type of disease

20. W/U for visceral disease • For visceral disease, the parasite can be detected through direct evidence (amastigotes in tissue) from peripheral blood, bone marrow, liver, or splenic aspirates. • The most sensitive method is splenic puncture, although iatrogenic complications can be serious, including potentially life-threatening hemorrhage. • In current practice, the high sensitivity and specificity of the recombinant K39 assay has generally made such invasive procedures unnecessary.

21. Cont’d • A variety of immunodiagnostic serologic tests have been developed to aid in the diagnosis of systemic leishmaniasis. However, the only successfully deployed serologic tests are limited to species of Leishmania that cause visceral disease • Considerable experience has been gained and success achieved with using bone marrow aspiratesfor cultivating the parasite or for looking for macrophages filled with amastigotes in the stained bone marrow aspirate smears

22. Hematologic tests • Complete blood cell (CBC) count • In patients with visceral leishmaniasis, the presence of (1) normocytic normochromic anemia, (2) leukopenia with decreased neutrophils and a relative monocytosis and lymphocytosis, and (3) thrombocytopenia may occur due to parasitic bone-marrow infiltration. The severity of pancytopenia may vary with only 1 or 2 cell lines decreased

23. Peripheral blood smear Amastigotes are revealed inside the circulating monocytes and neutrophils. However, these are often difficult to locate because of their small numbers • Liver function tests (LFTs) Patients with visceral leishmaniasis may exhibit mild elevations in alkaline phosphatase, aspartate aminotransferase (AST), and alanine aminotransferase (ALT) levels • Other tests Hypogammaglobinemia, circulating immune complexes, and rheumatoid factors are present in sera of most patients with visceral leishmaniasis.

24. Treatment • Factors to consider when planning the treatment of leishmaniasis include the • region of the world in which the infection was acquired, • the species of Leishmania • the site(s) and severity of the infection • host factors such as immune status and age.

25. Treatment • Indications for treatment of cutaneous leishmaniasisinclude • persistence for >6 months • location over a joint • presence of multiple (~5-10) or large (~4-5 cm) lesions

26. Treatment • Parenteral pentavalent antimonials (20 mg/kg/day IV or IMx 20 days ) are the treatment of choice for cutaneous and mucocutaneousleishmaniasis, whereas liposomal amphotericin B (3 mg/kg on days 1-5, 14 and 21) is preferred for visceral leishmaniasis • Others • Sodium stibogluconate(20 mg/kg/day IV or 1Mx 20 days) • Miltefosine (2.5 mg/kg/day PO (max 150 mg) x 28 days)

27. Alternative treatments • Paromomycin (Topically BID x 10-20 days) • Pentamidine (2-3 mg/kg IV or 1Mdaily or every other day x 4-7 doses) • Fluconazole (200 mg/day or 6-8 mg/kg/day PO x 6 weeks) • Liposomal amphotericin B (3 mg/kg on days 1-5, 14 and 21)

28. Treatment leishmaniasis in immunosuppressive patient

29. Reactivation of Cutaneous Leishmaniasis after Renal Transplantation: A Case ReportHossein Mortazavi,1Mehrnaz Salehi,1 and Kambiz Kamyab21Department of Dermatology, Tehran University of Medical Sciences, Razi Hospital,2013

30. Abstract • A 45-year-old man with reactivation of previously existing and subsiding cutaneous leishmaniasison his wrist and lower leg (shin) after renal transplantation was admitted to our dermatology service on March 2008. He presented to us with two huge tumoral and cauliflower-like lesions. Skin smear and histopathology of skin showed leishman bodies and confirmed the diagnosis. After renal transplantation, he received cyclosporine plus prednisolone to induce immunosuppression and reduce the probability of transplant rejection

31. Cont’d • The patient responded to 800 mg/day intravenous sodium stibogluconate for 3 weeks plus local cryotherapy. Systemic plus local therapy along with reducing the doses of immunosuppressive drugs led to improvement of lesions. Reactivation of leishmaniasis after immunosuppression has been rarely reported

32. Case 2 Isfahan , Drasilian et al , dermatology department 2012

33. 2. Case Report • A 45-year-old Iranian man with renal transplant and with two tumoral lesions was admitted to our dermatology ward on March 2008. The patient was suffering from chronic renal failure due to diabetes (non-insulin-dependent diabetes mellitus, NIDDM) for several years before this admission. • After admission to our dermatology department, he was treated with 800 mg/day IV sodium stibogluconate(Pentostam, pentavalent antimonials) for 3 weeks. In addition, his lesions were treated with local destructive cryotherapy; cryotherapy was applied by using the liquid nitrogen according to Asilian et al.. The patient responded favorably to the above treatment

34. Lipsosomal Amphotericin B for Treatment of Cutaneous LeishmaniasisGlenn Wortmann,*Michael Zapor, Roseanne Ressner, Susan Fraser, Josh2010

35. A retrospective review of patients receiving liposomal amphotericin B through the Walter Reed Army Medical Center for the treatment of cutaneous leishmaniasis during 2007–2009 was conducted • Sixteen (84%) of 19 experienced a cure with the initial treatment regimen. Three patients did not fully heal after an initial treatment course, but were cured with additional dosing. •  Acute infusion-related reactions occurred in 25% and mild renal toxicity occurred in 45% of patients

36. Conclusion • Although the optimum dosing regimen is undefined and the cost and toxicity may limit widespread use, liposomal amphotericin B is a viable treatment alternative for cutaneous leishmaniasis.

37. Usual Adult Dose for Leishmaniasis • Immunocompetent patients: 3 mg/kg/day IV on days 1 through 5, and days 14 and 21 • -Infuse over 120 minutes. • -If parasitic clearance is not achieved, a repeat course may be useful. • Immunocompromised patients: 4 mg/kg/day IV on days 1 through 5, and days 10, 17, 24, 31 and 38 • -Infuse over 120 minutes. • -If parasitic clearance is not achieved or relapse occurs, seek expert advice regarding further treatment

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