|Year : 2013 | Volume
| Issue : 3 | Page : 212-215
Cytological study of cutaneous lesions in HIV-infected patients
L Sushila Devi1, Supriya Laifangbam2, Nandakishore Singh3, Ellen Doris1
1 Department of Pathology, Jawaharlal Nehru Institute of Medical Sciences (JNIMS), Imphal, Manipur, India
2 Department of Microbiology, Jawaharlal Nehru Institute of Medical Sciences (JNIMS), Imphal, Manipur, India
3 Department of Dermatology, RIMS, Imphal, Manipur, India
|Date of Web Publication||19-Feb-2014|
L Sushila Devi
RIMS Colony, Lamphelpat, Qrt. No: V/4, Imphal - 795 004, Manipur
Source of Support: None, Conflict of Interest: None
Background: Early diagnosis of cutaneous lesions in HIV-infected patients is essential as most of these lesions are associated with significant morbidity and mortality. Objectives: To analyze the cutaneous lesions, the role of aspiration cytology in diagnosing these lesions and correlation with CD4 counts. Materials and Methods: This is a cross-sectional study of 34 cases of HIV sero-positive patients attending the cytology section of the Department of Pathology, Jawaharlal Nehru Institute of Medical Sciences (JNIMS), Imphal, Manipur over a period of 3 years (January 2009 to December 2011). The aspirated materials were stained with May-Grunwald Giemsa (MGG)/Leishman stain, and special stains were also done whenever necessary. Cultural confirmation in fungal lesions (ten cases) and serological tests in cryptococcal lesions were also done. Histological examinations were performed in case of neoplastic lesions (2 cases) and cases which were inconclusive by fine needle aspiration cytology (FNAC). History of receiving anti-retroviral therapy and data for CD4 count in all the cases were also analyzed. Results: Majority of the cases (91.2%) could be diagnosed by FNAC. The patterns of skin lesions were fungal (61.8%), viral (14.7%), Kaposi sarcoma (8.8%), tuberculosis (2.9%) and eosinophilic folliculitis (2.9%) respectively. Conclusion: FNAC is a rapid, safe, useful, inexpensive, and patient-friendly procedure in detecting various cutaneous lesions in HIV-infected patients.
Keywords: Cutaneous lesions, CD4 count, FNAC, HIV
|How to cite this article:|
Devi L S, Laifangbam S, Singh N, Doris E. Cytological study of cutaneous lesions in HIV-infected patients. J Med Soc 2013;27:212-5
| Introduction|| |
Skin manifestations including those of opportunistic infections are common among HIV-infected patients, which are a burdensome stigma for the patient and also, a challenging task for the health care providers. Skin is often the first and only organ affected during most of the course of HIV disease. , HIV infects predominantly CD4+ cells predisposing the patients to numerous opportunistic infections, malignancies, and neurologic diseases.  Kaposi's sarcoma is the most common AIDS-associated skin cancer.  Many skin lesions in HIV-infected patients have similar clinical presentations and so, a proper diagnosis is highly essential to manage the case.
| Materials and Methods|| |
This study consisted of 34 HIV-infected patients referred to the cytology section of Department of pathology, JNIMS, Imphal, Manipur with various skin lesions during the period of 3 years w.e.f. from Jan'09. FNAC samples (single/multiple) were taken from the lesions using 24G needle mounted on a 10 c.c. syringe. The aspirated smears were routinely stained with May-Grunwald Giemsa (MGG) /Leishman stain. Special stains like periodic acid Schiff (PAS) and /or Gomori'smethenamine silver (GMS) stain and Ziehl-Neelsen (ZN) stain were also done when necessary. Cultural confirmation using Sabouraud dextrose agar (SDA) was obtained in ten of the cases diagnosed as fungal lesion by FNAC. The aspirate which was inoculated onto SDA media was incubated at 25°C upto 4 weeks. In case of P. marneffei (colonies with red pigment), further incubation at 37°C for 4-7 days was done to observe the mold-to-yeast conversion. Serological test (Latex agglutination test) for cryptococcal antigen was also done in all cases with cryptoccocal lesions. Histopathological examination were also done in two cases of Kaposi's sarcoma diagnosed by FNAC using excisional biopsy with subsequent histological sections stained by H&E stain and in cases which were inconclusive by FNAC.
| Results and Observations|| |
In this study, HIV seropositive patients were mostly from middle age group (31-45 yrs) with a mean age of 38.38 ± 6.9 years. There were 23 males (67.6%) and 11 females (32.4%) with a male to female ratio of 2.1:1 [Table 1]. All cases had severe immune-suppression with CD4 counts < 250/μl, and mean CD4 count was 80.53 ± 66.54 cells/μl [Table 2]. Majority of the cases (n = 22, 64.7%) were not on anti-retroviral therapy; nine cases (26.5%) gave history of starting treatment only recently, and a few (n = 3, 8.8%) were on irregular treatment. The most common cutaneous lesion was of fungal origin (n = 21, 61.8%); others were viral (n = 5, 14.7%), Kaposi's sarcoma (n = 3, 8.8%), eosinophilic folliculitis (n = 1, 2.9%), tuberculous lesion (n = 1.2.9%) [Table 3]. The fungal lesions had different rate of growth as well as colony characteristics. P. marneffei is the commonest fungal pathogen (n = 18, 52.9%) followed by Cryptococcus (n = 2, 5.9%) and Histoplasma capsulatum (n = 1, 2.9%). P. marneffei in the stained aspiration smears appeared as numerous yeast-like tissue forms, some of them showing prominent central septum (bars) indicating multiplication by fission [Figure 1] and [Figure 2], and this finding aids in the differentiation from Histoplasma capsulatum, which divides by budding. Cryptococcus appears as budding yeast cells ranging from 5-20 μm in size [Figure 3]. All the fungal pathogen showed positivity for PAS and/or GMS stain. Culture was done in 10 cases diagnosed as fungal lesion by FNAC (P. marneffei - 6, Cryptococcus - 2, H. capsulatum - 2), which correlates with the cytological diagnosis in nine of the cases [Table 4]. Molluscum contagiosum (n = 4, 11.8%) was identified by the presence of numerous Molluscum bodies, which are diagnostic of these lesions. A diagnosis of verrucous vulgaris was made in one case, who also suffers from cryptococcal meningitis from the clinical appearance and the cytological findings of viropathic effects, though histopathological confirmation could not be done.
|Figure 3: Photomicrograph of yeast cells of Cryptococcus (Leishman, X1000)|
Click here to view
Kaposi's sarcoma (n = 3, 8.8%), which was clinically diagnosed, showed spindle-shaped cells with elongated hyperchromatic nuclei and coarse nuclear chromatin in a background of blood [Figure 4]. Histopathological examination (HPE) was done in two of the cases, which correlates with the cytological diagnosis [Table 4].
One case (2.9%) each of eosinophilic folliculitis and cutaneous tuberculosis were among the cases studied. Aspiration smears from a case of eosinophilic folliculitis showed mixed inflammatory cells, eosinophils forming about 50% with no AFB or fungal elements, whereas the cutaneous tuberculosis showed a few neutrophils in a background of massive caseation necrosis with numerous AFB on Z-N stain.
FNAC was inconclusive in 3 cases (8.8%), and HPE show features of non-specific maculo-papular eruptions in two of the cases and fungal (P. marneffei) pathology in one case.
| Discussion|| |
A variety of cutaneous manifestations can occur in HIV-infected patients producing significant morbidity, and some dermatologic manifestations in such patients also acts as marker of disease progression with decline in immune function. , As many as 90% of HIV-positive patients may develop one or more skin lesions during the course of their illness.  The spectrum of skin diseases encompasses non-infective and infective dermatoses, adverse drug reactions, and dermatologic neoplasms. Various viral, bacterial, fungal, protozoal, and arthropod infections may produce muco-cutaneous lesions in patients with HIV infection. Non-infectious cutaneous disorders like seborrheic dermatitis, psoriasis, photodermatitis, eosinophilic folliculitis etc. are also common in HIV infection and can occur at all stages of the disease. The relative frequencies of specific opportunistic diseases may vary in different countries. In the context HIV infection, a variety of systemic fungal diseases including cryptococcosis, histoplasmosis, and P. marneffei can disseminate and produce skin lesions, and fungal diseases have been one of the most relevant diagnosis in relation to AIDS.  P. marneffei, the most common fungal pathogen in our study, is not seen/very rarely seen in other parts of India. Low CD4 count in P. marneffei infection in HIV-infected patients have also been observed by many workers. , It is the third most common opportunistic infection in patients with AIDS in S.E. Asian countries and its high prevalence in Manipur may be due to the common geographic, ethnic, ecologic, and climatic condition with the endemic S.E. Asian countries. Histoplasma capsulatum, another important opportunistic fungus in relation to HIV infection, was also seen in one patient who had a CD4 count of 71 cells/μl. Similar lesions with low CD4 count have also been observed by others.  Cutaneous lesions occur in 6% of patients with disseminated histoplasmosis, and it may rarely be the presenting sign.  Two patients had disseminated cryptococcosis with cutaneous involvement having a CD4 count of 22 and 92 cells/μl respectively. Skin lesions in disseminated cryptococcosis indicate a poor prognosis. However, early recognition and treatment would improve survival. Cutaneous lesion may be seen in 10-20% of disseminated cryptococcosis. , It generally occurs in patients with CD4 count <100 cells/μl.  Primary cutaneous lesion do occur rarely.
As there is gradual deterioration of immune system, HIV-infected patients are prone to develop numerous cutaneous viral diseases particularly Herpes, HPV, and Molluscum contagiosum.  Out of the four cases of Molluscum contagiosum observed in this study, one case had an associated cryptococcosis. Molluscum contagiosum develops often in advanced HIV infection with a prevalence rate of 5-18% among such people. A case of verruca vulgaris with an associated cryptomeningitis who had a CD4 count of 11 cells/μl was also observed. Defective cell-mediated immunity predisposes to the development of some types of warts, and in the context of HIV infection, a variety of papilloma virus has been reported.
Kaposi's sarcoma, an angio-proliferative neoplasm derived from lymphatic endothelium, is the most common HIV-related malignancy though melanoma, SCC, and BCC have also been reported in these patients.  Three cases were diagnosed with Kaposi's sarcoma, each case having a CD4 count of <200 cells/μl. Similar findings were also observed by Stefan et al. and others.  Over 95% of Kaposi sarcoma lesion have been associated with HHV-8. 
Tuberculosis is the common cause of death in AIDS patients, and its prevalence is increasing with HIV infection with many reported multi-drug-resistant cases. A case of cutaneous tuberculosis presenting as abscess that was treated earlier for pulmonary tuberculosis was observed in this study. Tuberculosis in most AIDS patient is due to reactivation of previously acquired tuberculosis, and frequency of extra-pulmonary tuberculosis is more in patients with severe immunodeficiency. Association of tuberculosis with low CD4 count was also observed by Mbuagbaw et al. 
Eosinophilic folliculitis, a rare dermatological condition, was diagnosed in a case that had a CD4 count of 198 cells/μl. Its incidence is increasing with HIV infection and is more commonly seen in patients with CD4 count <200 cells/μl.
| Conclusion|| |
This study shows that certain dermatological manifestations in HIV-infected patients occur more frequently with progression of HIV and decline in immune function. Therefore, early diagnosis and treatment of these patients can improve the quality of life in such patients. Since majority of the patients are from remote areas who get to know their HIV status very late with a very low CD4 counts, more emphasis should be given on health education and voluntary counseling etc. in these areas for an early HIV diagnosis. Compared to tissue biopsy and culture, FNAC is a rapid and useful procedure allowing early institution of therapy, which is of particular importance in immune-compromised patients. However, more studies involving larger sample sizes may give better statistical data.
| References|| |
|1.||Tschachler E, Bergstresser PR, Sting IG. HIV related skin diseases. Lancet 1996;348:659-63. |
|2.||Goldstein B, Berman B, Sukenik E, Frankel SJ. Correlation of skin disorders with CD4 counts in patients with HIV/AIDS. J Am Acad Dermatol 1997;36:262-4. |
|3.||Xiaowei Xu, Erickson L, Chen L, Elder DE. Diseases caused by viruses. Lever's Histopathology of the skin, 10 th ed. Philadelphia: Lippincott William & Wilkins; 2009. p. 659. |
|4.||Coopman SA, Johnson RA, Plat R, Stern R. Cutaneous diseases and drug reactions in HIV infection. N Engl J Med 1993;328:1670-4. |
|5.||Hartshorne ST. Dermatological disorders in Johannesburg, South Africa. Clin Exp Dermatol 2003;28:661-5. |
|6.||Marques SA, Robles AM, Tortorano AM, Tuculet MA, Negroni R, Mendes RP. Mycosis associated with AIDS in third world. Med Mycol 2000;38:269-79. |
|7.||Wu TC, Chan JW, Ng CK, Tsang DN, Lee MP, Li PC. Clinical presentation and outcome of P. marneffei infection: A series from 1994-2004. Hong Kong Med J 2008;14:103-9. |
|8.||Huynh TX, Nguyen HC, DinhNyuyen HM, Do MT, Odermatt-Biays S, Degremont A, et al. Penicilium marneffei infection and AIDS. A review of 12 cases reported in the tropical disease centre, Ho Chi Minh City (Vietnam). Sante 2003;13:149-53. |
|9.||Fauci AS, Lane HC. Human Immunodeficiency Virus disease: AIDS and related disorders. In: Harrison's Principles of Internal Medicine, 17 th ed. New York: McGraw Hill Companies Inc.; 2008. p. 1182-86. |
|10.||Hinshaw M, Longley BJ. Fungal diseases, Lever's histopathology of the skin, 10 th ed. Philadelphia: Lippincott William & Wilkins; 2009. p. 611. |
|11.||Vasanthi S, Padmavathy BK, Gopal R, Sundaram RS, Manoharan G. Cutaneous cryptococcosis among HIV infected patients. J Med Microbiol 2002;20:165-6. |
|12.||Capoor MR, Khanna G, Malhotra R, Verma S, Nair D, Deb M, et al. Disseminated cryptococcosis with necrotizing fascitis in an apparently immune-competent host: A case report. Med Mycol 2008;46:269-73. |
|13.||Costner M, Cockerell CJ. The changing spectrum of the Cutaneous manifestations of HIV disease. Arch Dermatol 1998;134:1290-2. |
|14.||Stefan DC, Stones DK, Wainwright L, Newton R. Kaposi's sarcoma in South African children. Pediatr Blood Cancer 2011;56:392-6. |
|15.|| Singh H, Singh P, Tiwari P, Dey V, Dulhani N, Singh A. Dermatological manifestation in HIV infected patients at a tertiary care hospital in a tribal region of Chhattisgarh, India. Indian J Dermatol 2009;54:338-41. |
|16.||Martinelli PT, Tyring SK. Human Herpes Virus 8. Dermatol Clin 2002;20:307-14. |
|17.||Mbuagbaw J, Afetane G, Kam MN. Association between CD4 counts and clinical presentation among HIV/AIDS patients in Cameroon. J Med Sci 2006;6:843-7. |
[Figure 1], [Figure 2], [Figure 3], [Figure 4]
[Table 1], [Table 2], [Table 3], [Table 4]