title: Comparative histological and immunohistochemical changes of dry type cutaneous leishmaniasis after administration of meglumine antimoniate, imiquimod or combination therapy.
abstract: BACKGROUND
  This study compared histological and immunohistochemical changes of cutaneous leishmaniasis treated with meglumine antimoniate, imiquimod, and the combination of both therapies.
  
  
  METHODS
  Single blind clinicopathological studies of fifteen patients with old world cutaneous leishmaniasis in Kerman, Iran were included. A total of four patients received a combination of imiquimod (5% cream) and intra-lesional meglumine antimoniate weekly for four weeks. Monotherapy with imiquimod was given to seven patients and four patients were treated with meglumine antimoniate intralesionally. Histological confirmation was performed before and during therapy. Semi-quantitative histological parameters such as numbers of mixed inflammatory cells (cells/mm(2)) and percentages of Langerhans cells (CD1a+), T-cells (CD3+), B-cells (CD20+), and macrophages (CD68+) were calculated immunohistochemically in the dermis and adjacent epidermis.
  
  
  RESULTS
  Topical imiquimod significantly reduced mean histiocytic cellular aggregation size (P<0.05). Meglumine antimoniate reduced parasite load and infected activated histiocytes in the dermis (P<0.05). Meglumine antimoniate therapy decreased epidermal CD3+ lymphocytes but increased them in the dermis, within the granulomas (P<0.05). During topical application of imiquimod a depletion of CD1a+ dendritic cells in the epidermis (P<0.05) and slight predominance of dendritic cells in the dermis were observed. Combined therapy and imiquimod monotherapy decreased CD68+ macrophages in the dermis (P<0.05).
  
  
  CONCLUSIONS
  Meglumine antimoniate decreases parasite load with considerable effect on up-regulation of T-cells, which demonstrates that meglumine antimoniate works as parasitocidal and immunomodulator, which could be a first line of treatment. Imiquimod accentuates the host immune response and reduces granuloma size which could be effective immunomodulator for combination therapy. Monotherapy of imiquimod is less effective than the two other regimens in decreasing parasite load, inflammation and congestion at the inoculated site.
authors: Dermatology Department, Afzalipour Medical School, Kerman University of Medical Science, Kerman, Iran. meymandi_s@hotmail.com
authors: Simin
authors: S
authors: Shamsi Meymandi
authors: Abdolreza
authors: A
authors: Javadi
authors: Shahriar
authors: S
authors: Dabiri
authors: Manzumeh
authors: M
authors: Shamsi Meymandi
authors: Mehrdad
authors: M
authors: Nadji
mesh_terms: D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000634:Aminoquinolines / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D018949:Antigens, CD1 / Q000032:analysis; D018951:Antigens, CD20 / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D000981:Antiprotozoal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D001402:B-Lymphocytes / Q000276:immunology; D017252:CD3 Complex / Q000032:analysis; D002648:Child; D020405:Dermis / Q000276:immunology; D004359:Drug Therapy, Combination; D004817:Epidermis / Q000276:immunology; D005260:Female; D006801:Humans; D000077271:Imiquimod; D007492:Iran; D007801:Langerhans Cells / Q000276:immunology; D007895:Leishmania tropica / Q000276:immunology*; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy / Q000276:immunology* / Q000473:pathology*; D018655:Lymphocyte Count; D008264:Macrophages / Q000276:immunology; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000627:therapeutic use*; D000077485:Meglumine Antimoniate; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D059208:Parasite Load; D016037:Single-Blind Method; D013601:T-Lymphocytes / Q000276:immunology; D055815:Young Adult; D000097382:CD68 Molecule
chemical_list: D000276:Adjuvants, Immunologic; D000634:Aminoquinolines; D015703:Antigens, CD; D018949:Antigens, CD1; D018951:Antigens, CD20; D015214:Antigens, Differentiation, Myelomonocytic; D000981:Antiprotozoal Agents; D017252:CD3 Complex; D000077271:Imiquimod; D008536:Meglumine; D000077485:Meglumine Antimoniate; D009942:Organometallic Compounds; C419393:CD1a antigen; C067980:CD68 antigen, human; D000097382:CD68 Molecule