| Abstract|| |
Background: Cutaneous leishmaniasis (CL) is a parasitic cutaneous infection caused by Leishmania parasite. The histopathology is usually granulomatous in nature. Aims: The aim of the present study is to elucidate the histology of CL and evaluate the presence and the frequency of panniculitis among the affected patients. Settings and Design: Case series interventional study. Materials and Methods: Thirty-five patients with CL were diagnosed clinically between December-2012 and May-2013. Diagnostic confirmation established by smears, culture, and polymerase chain reaction (PCR). The histopathological assessment was carried out to study the general pathology and to look for the presence of panniculitis. Statistical Analysis Used: Simple statistics utilized via SPSS version 16.0 (SPSS, Inc., Chicago, USA). Results: Eighteen women and 17 men with CL were enrolled in the present work with a mean duration of their disease was 3 months. The results of the diagnostic tests were as follow: The smear was positive in 21 (60%) of cases, Leishman-Donovan (LD) bodies were seen in 7 (20%) patients, culture was positive in 24 (68%), and PCR was positive in 32 (91.4%) patients. The epidermal changes included acanthosis, pseudoepitheliomatous hyperplasia, ulceration, focal spongiosis, and interface dermatitis while the dermal changes were dependent on the spectrum of the disease, so in the ulcerative lesions there was lymphohistiocytic infiltration with foci of plasma cells and sometimes aggregate of LD bodies, whereas in the dry lesions the pathology is mainly of epithelioid granuloma. Panniculitis was seen in 16 (46%) cases as a diffuse lymphohistiocytic infiltration of both the septum and lobules of the subcutaneous layer of the skin. Conclusion: Panniculitis is an important feature of CL that must be differentiated from other diseases that can simulate CL such as chronic skin infections, Discoid lupus erythematosus, and cutaneous lymphoma.
Keywords: Cutaneous biopsy, cutaneous leishmaniasis, panniculitis
|How to cite this article:|
Sharquie KE, Hameed AF, Noaimi AA. Panniculitis is a common unrecognized histopathological feature of cutaneous leishmaniasis. Indian J Pathol Microbiol 2016;59:16-9
|How to cite this URL:|
Sharquie KE, Hameed AF, Noaimi AA. Panniculitis is a common unrecognized histopathological feature of cutaneous leishmaniasis. Indian J Pathol Microbiol [serial online] 2016 [cited 2020 Feb 28];59:16-9. Available from: http://www.ijpmonline.org/text.asp?2016/59/1/16/178216
| Introduction|| |
Cutaneous leishmaniasis (CL) is an endemic parasitic skin disease that caused by Leishmania tropica and Leishmania minor in patients of Middle East residency.  The disease is transmitted by a bite of sandfly that result in the inoculation of the parasite into the human skin.  For the proof of diagnosis, it requires the demonstration of the parasite in the host tissues or the culture. Meanwhile, the histological diagnosis is considered as important corner in the evaluation of the disease especially in cases of granulomatous pathology. 
Infectious panniculitis is an inflammation of the subcutaneous tissue which caused by a variety of pathogens such as bacteria, fungi, and parasites.  However, only few case reports had demonstrated that CL can cause panniculitis.  The aim of the present study is to evaluate the histopathology of CL with special emphasis on the presence of panniculitis through utilizing a deep skin biopsies to include the subcutaneous tissue in the studied specimens.
| Materials and methods|| |
This case series interventional study has involved 35 patients with CL; all of them had been diagnosed clinically by two dermatologists. Their ages ranged from 8-58 years. Multiple smears were obtained from the boundaries of the lesions by dental broach, and deep incisional biopsies reaching the subcutis were taken from the most indurated border of the lesions by using surgical blade sized 11. The paraffin-embedded specimens were stained with hematoxylin-eosin (H and E) stain, and Novy-MacNeal-Nicolle culture medium was done in all cases. Polymerase chain reaction (PCR), using mini-exon as a DNA target-based method, was performed to confirm the diagnosis for all patients.  Statistical analysis was performed using SPSS version 16.0 (SPSS, Inc., Chicago, IL, USA). Ethical approval has obtained from the higher Board for Medical Specializations, and all patients gave their consent to participate in this work after full education about the nature of the study.
| Results|| |
Thirty-five patients (18 women and 17 men) with diagnosis of CL had been evaluated. Ten patients had single lesion while 25 patients had multiple lesions ranging from 2-7. The duration of the disease ranged from 1-7 months with a mean duration of 3 months. The smears were positive for the amastigote in 21 (60%) of cases, Leishman-Donovan (LD) bodies were seen in 7 (20%) of histopathology sections, culture demonstrated the parasite in 24 (68%) patients while PCR was positive in 32 (91.4%) patients. L. tropica (60%) and L. minor (40%) were the two species which had been recognized by PCR in this study.
The histopathology of CL was variable according to the age of lesions and the type whether it is ulcerative or dry, but the general picture was that of a spectrum with one end as diffuse and dense lymphohistiocytic infiltration with foci of plasma cells while, on the other end, there was the full development of epithelioid granuloma with sparse or no plasma cells [Figure 1]. Some of these granulomas have a tendency for peri-appendgeal involvement, and sometimes even with intra-follicular invasion of the mononuclear cellular infiltrate [Figure 2].LD bodies were seen in the upper dermis in 7 (20%) cases, particularly in the early ulcerative lesions, as small round or oval bodies which stain pale blue with Giemsa or a pale blue-gray with H and E [Figure 3]. The histopathological changes were summarized in [Table 1].
|Figure 1: Epidermal changes showing acanthosis and interface dermatitis while the dermis has diffuse lymphohistiocytic infiltration with Langhans giant cell formation (H and E, ×100)|
Click here to view
|Figure 3: Leishman - Donovan bodies appearing as metachromatic bodies both inside and outside the macrophages with aggregate of plasma cells (H and E, ×1000)|
Click here to view
Panniculitis was seen in 16 (46%) cases as a diffuse lymphohistiocytic infiltration of both the septum and lobules of the fatty layer producing a picture of mixed septal and lobular panniculitis [Figure 4]. LD bodies were absent in all sections which contained panniculitis whereas the plasma cells were present in a localized aggregate in the panniculitis lesions. Panniculitis was more prevalent among dry lesions (62.5% vs. 37.5% in ulcerative lesions), multiple clinical lesions (75% vs. 25% in single lesions) over the upper limbs of the patients with CL (69% vs. 31% in lower limb lesions). The occurrence of panniculitis in relation to the different clinical variables is shown in [Table 2].
|Figure 4: Mixed type panniculitis with granulomatous infiltration of the septum and lobules of the panniculus (H and E, ×100)|
Click here to view
| Discussion|| |
CL is an important health problem in countries of the Middle East.  The main species isolated in CL are L. tropica and L.minor causing ulcerative and dry leishmaniasis, respectively.  The histological diagnosis is often difficult where the demonstration of the parasite in the smears and the tissue specimens is challenged by the small size of the amastigote and the focal distribution of them in a few aggregates rather than in a homogenous distribution. 
The general histopathology of the present work was comparable to previous studies from different regions of the world. ,,
The main histologic findings, in the present study, are a spectrum of granulomatous dermatitis, the presence of plasma cells (usually in foci), and the presence of LD bodies in the upper dermis but not on the panniculus of the specimens [Figure 1] and [Figure 3]. Moreover, we demonstrated that the granuloma formation has tendency to distribute around the appendageal structures, especially the hair follicle and the eccrine glands which in some cases associated with infiltration of the hair follicle by the inflammatory cells producing picture similar to folliculitis [Figure 2].
In the present work, all specimens were deep incisional biopsies which considered as important criteria for its evaluation. Hence, we were able to demonstrate for the first time that panniculitis is a constant feature of leishmaniasis pathology where it was seen in 16 (46%) of cases.
The inflammatory reaction was seen both in the septum and the lobules of the panniculus with the characteristic presence of aggregate of plasma cells and the absence of LD bodies in the subcutis [Figure 4]. Therefore, we think that the panniculitis seen in CL is a phenomenon that can be explained as an extension of the severe inflammatory process rather than a direct infection of the parasite to the fatty layer of the skin.
The histologic differential diagnosis of CL includes many infectious diseases of the skin that causes granulomatous reaction such as cutaneous tuberculosis, leprosy, tertiary syphilis, and deep fungal infection.  PCR is the most specific and sensitive test used to exclude all these chronic skin infections and reach a definitive diagnosis of CL. 
The presence of panniculitis must be considered in evaluation of any inflammatory or infectious panniculitis, especially in the endemic regions. As the sensitivity of different diagnostic techniques (including smears and culture) are variable, PCR for infection panel is mandatory to carry out in all cases of panniculitis with unestablished diagnosis.
| Conclusion|| |
Panniculitis is an important feature of CL, and its presence must not lead the pathologist to misdiagnose it with other infectious or inflammatory diseases that characterized by panniculitis.
Financial support and sponsorship
Department of Dermatology, University of Baghdad, College of Medicine.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Aljeboori TI, Evans DA. Leishmania
spp. in Iraq. Electrophoretic isoenzyme patterns. II. Cutaneous leishmaniasis. Trans R Soc Trop Med Hyg 1980;74:178-84.
Radentz WH. Leishmaniasis: Clinical manifestations, immunologic responses, and treatment. J Assoc Mil Dermatol 1987;13:15-21.
Kalter DC. Laboratory tests for the diagnosis and evaluation of leishmaniasis. Dermatol Clin 1994;12:37-50.
Requena L, Yus ES, Kutzner H. Disorders of subcutaneous tissue. In: Wolf K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DA, editors. Fitzpatrick's Dermatology in General Medicine. 7 th
ed. New York: McGraw Hill Publishers; 2008. p. 579.
Sharquie KE, Hameed AF. Panniculitis is an important feature of cutaneous leishmaniasis pathology. Case Rep Dermatol Med 2012;2012:612434.
Marfurt J, Nasereddin A, Niederwieser I, Jaffe CL, Beck HP, Felger I. Identification and differentiation of Leishmania
species in clinical samples by PCR amplification of the miniexon sequence and subsequent restriction fragment length polymorphism analysis. J Clin Microbiol 2003;41:3147-53.
Jaber SM, Ibbini JH, Hijjawi NS, Amdar NM, Huwail MJ, Al-Aboud K. Exploring recent spatial patterns of cutaneous leishmaniasis and their associations with climate in some countries of the Middle East using geographical information systems. Geospat Health 2013;8:143-58.
Sharquie KE, Najim RA. Disseminated cutaneous leishmaniasis. Saudi Med J 2004;25:951-4.
Sharquie KE, Hassen AS, Hassan SA, Al-Hamami IA. Evaluation of diagnosis of cutaneous leishmaniasis by direct smear, culture and histopathology. Saudi Med J 2002;23:925-8.
Koçarslan S, Turan E, Ekinci T, Yesilova Y, Apari R. Clinical and histopathological characteristics of cutaneous Leishmaniasis in Sanliurfa City of Turkey including Syrian refugees. Indian J Pathol Microbiol 2013;56:211-5.
Barral A, Costa JM, Bittencourt AL, Barral-Netto M, Carvalho EM. Polar and subpolar diffuse cutaneous leishmaniasis in Brazil: Clinical and immunopathologic aspects. Int J Dermatol 1995;34:474-9.
Venkataram M, Moosa M, Devi L. Histopathological spectrum in cutaneous leishmaniasis: A study in Oman. Indian J Dermatol Venereol Leprol 2001;67:294-8.
Mehregan DR, Mehregan AH, Mehregan DA. Histologic diagnosis of cutaneous leishmaniasis. Clin Dermatol 1999;17:297-304.
Foulet F, Botterel F, Buffet P, Morizot G, Rivollet D, Deniau M, et al.
Detection and identification of Leishmania
species from clinical specimens by using a real-time PCR assay and sequencing of the cytochrome B gene. J Clin Microbiol 2007;45:2110-5.
Khalifa E Sharquie
Medical Collection Office, P. O. Box 61080, Baghdad 12114
Source of Support: None, Conflict of Interest: None
Clinical trial registration IRCT2013040812758N2
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2]