|Year : 2015 | Volume
| Issue : 3 | Page : 439-442
Pancytopenia and cutaneous cryptococcosis as an indicator disease of acquired immune deficiency syndrome
R Khuraijam1, P Lungran1, K Yoihenba2, RS Laishram3, P Pukhrambam1
1 Department of Microbiology, Regional Institute of Medical Sciences, Imphal, Manipur, India
2 Department of Medicine, Regional Institute of Medical Sciences, Imphal, Manipur, India
3 Department of Pathology, Regional Institute of Medical Sciences, Imphal, Manipur, India
|Date of Submission||29-Oct-2014|
|Date of Acceptance||20-Jan-2015|
|Date of Web Publication||12-Jun-2015|
Department of Microbiology, Regional Institute of Medical Sciences, Imphal, Manipur
Source of Support: Department of Biotechnology, Ministry of Science
and Technology, New Delhi, Conflict of Interest: None
We present a case of pancytopenia and cutaneous cryptococcosis in a young girl with no complaints of fever, headache and vomiting. Fine-needle aspiration cytology and further investigation for pancytopenia revealed presence of Cryptococcus in skin and bone marrow aspirates. Fungal cultures of the skin aspirates, blood and bone marrow confirmed cryptococcal infection. Counselling and human immunodeficiency virus (HIV) test revealed the status of the patient to be retropositive. Although meningitis is the commonest manifestation of cryptococcosis among HIV-infected patients, rare cutaneous manifestation with pancytopenia but with no meningeal signs indicate the HIV status in an endemic area of penicilliosis, Manipur.
Keywords: Cutaneous cryptococcosis, human immunodeficiency virus, pancytopenia
|How to cite this article:|
Khuraijam R, Lungran P, Yoihenba K, Laishram R S, Pukhrambam P. Pancytopenia and cutaneous cryptococcosis as an indicator disease of acquired immune deficiency syndrome. Indian J Med Microbiol 2015;33:439-42
|How to cite this URL:|
Khuraijam R, Lungran P, Yoihenba K, Laishram R S, Pukhrambam P. Pancytopenia and cutaneous cryptococcosis as an indicator disease of acquired immune deficiency syndrome. Indian J Med Microbiol [serial online] 2015 [cited 2019 Jan 22];33:439-42. Available from: http://www.ijmm.org/text.asp?2015/33/3/439/158586
| ~ Introduction|| |
Disseminated cryptococcosis caused by Cryptococcus neoformans is a life-threatening opportunistic infection among immunosuppressed individuals. It is one of the commonest acquired immune deficiency syndrome (AIDS)-defining diseases, more so in sub-Saharan Africa and India.  Besides meningitis, disseminated infection can involve any other anatomic sites such as skin, eyes, genitourinary tract, gastrointestinal tract and abdominal cavity. Approximately, 15-20% of human immunodeficiency virus (HIV)-infected patients with meningeal cryptococcosis may have skin involvement. But, cutaneous manifestation with no apparent signs of meningeal involvement is a rare entity occurring in only about 6% of already diagnosed HIV-infected cases. Such cutaneous lesion as presenting sign of AIDS is rare in literature. On the other hand, infectious diseases including cryptococcosis may be the cause of pancytopenia. The more important and common cause of pancytopenia are aplastic anaemia, myelodysplastic syndrome, leukaemia, systemic lupus erythematosus, etc., before zeroing into infective causes such as cryptococcosis. A complete investigative work-up is essential when a young, apparently healthy-looking patient present with pancytopenia. Presence of skin lesions may provide the first evidence of disseminated infection and indicate a poor prognosis. However, earlier recognition and treatment would improve survival. , Manipur is an endemic region of penicilliosis, an indicator disease of AIDS and majority of them present with skin manifestations.  We describe a rather unusual and rare cutaneous manifestation of disseminated cryptococcosis with pancytopenia mimicking disseminated penicilliosis in a previously undiagnosed retropositive patient.
| ~ Case Report|| |
A 21-year-old female patient presented with generalized weakness for 1 month and she noticed multiple skin rashes and small papules in last 2 weeks. Some of these papules were having central necrosis [Figure 1]. There was no history of fever, cough, diarrhoea, headache or altered sensorium. Patient had history of herpes zoster infection about 6 months back. There was no history of any previous chronic illness. A non-tender soft hepatosplenomegaly was noted. Clinical examination of respiratory, cardiovascular and central nervous system was within normal limit.
Haematological investigations showed mild pancytopenia with Hb - 9.0 gm%, total leukocyte count (TLC) - 2800 cells/cu mm, platelet count of 80,000/cu mm and erythrocyte sedimentation rate (ESR) of 150 mm/1 st hr. Liver function test (LFT) showed elevated aspartate aminotransferase (AST) of 142 IU and Alanine transaminase (ALT) of 372 IU. Urine R/E, kidney function test (KFT) and chest X- ray were within normal limits. Fine-needle aspiration cytology of the skin papules revealed clumps of yeast cells with marked capsule. Aspirated samples from skin papules were subjected to examination by India ink preparation, Giemsa stain and Meyer's mucicarmine stain and it showed presence of Cryptococcus spp. [Figure 2] and [Figure 4]. Bone marrow examination as part of investigation for pancytopenia revealed dysplastic features in cell series with macrophage aggregates suggesting disseminated Kochs and presence of Cryptococcus spp. [Figure 3]. After counselling as per National AIDS Control Organisation guidelines, the patient was tested for HIV antibody. Retro-viral antibodies was positive and her CD4 count was 58 cell/cu mm. The serum cryptococcal latex agglutination test (CALAS, Meridian Diagnostics, Cincinnati, Ohio, USA) was positive, with a titre of 1:100. Sputum for acid fast bacilli was negative. Serological testing for hepatitis B surface antigen (HBsAg) and hepatitis C virus (HCV) antibody was negative.
|Figure 2: Giemsa stained smear of skin aspirate showing encapsulated Cryptococcus (×1000)|
Click here to view
|Figure 3: Giemsa stained bone marrow smear showing a single Cryptococcus (×1000)|
Click here to view
|Figure 4: Mayer mucicarmine stained skin aspirate showing a budding Cryptococcus|
Click here to view
Fungal culture of skin aspirate, blood, urine and bone marrow on Sabouraud dextrose agar and Bird seed agar showed growth of Cryptococcus spp. The isolate was positive for urease test and inositol assimilation. Species identiﬁcation was performed by sub-culture on canavanine glycine bromothymol blue (CGB) to differentiate C. neoformans from C. gatti. After 5 days of incubation at 25°C, the CGB media showed no change in colour. Thus, the isolate was characterized as C. neoformans. A serotype differentiation of the isolate was conducted using a creatinine dextrose bromothymol blue thymine (CDBT) medium. On CDBT medium, after 5 days of incubation at 28°C, pale colonies with no apparent colour effect on the medium were obtained, thereby confirming the isolate to be C. neoformansvar. grubii (serotype A). The identity of the isolate was also confirmed as Cryptococcus neoformans with the automated Vitek 2 compact system [bioMerieux Inc., (Durham, NC) USA]. The antifungal susceptibility of the isolate was determined using the AST- YS06 Vitek 2 card (bioMerieux) and it was sensitive to flucytosine, fluconazole, amphotericin B and voriconazole with a minimum inhibitory concentration (MIC) values of 4 μg/ml, 2 μg/ml, 1 μg/ml and 0.5 μg/ml, respectively.
Patient was managed by intravenous administration of amphotericin B, 0.6 mg/kg/day and followed by tab. Fluconazole 400 mg/day in divided doses. Anti-tubercular therapy (ATT) was initiated after 3 days of antifungal therapy. Three units of blood were transfused during her hospital stay. Three weeks after admission, with improved general condition and control of OIs, 1 st line antiretroviral drugs (ART) was initiated. After 4 weeks, patient was discharged with ART, ATT, fluconazole, 400 mg daily and other supportive treatment. At the time of discharge, haemoglobin was 10 gm%, total cell count was 4500/cu mm and platelet count was 1 lakh/cu mm and there was marked improvement of cutaneous lesions.
On follow-up after 4 months, patient was feeling much better and has gained weight with CD4 count of 152 cells/cu mm. During the recent follow-up after 10 months of diagnosis, the patient has gained weight by 10 kg, with good adherence to 1 st line ART and her CD4 count was 129 cells/cu mm. She is continuing with prophylactic antifungal therapy, attending college with normal day-to-day activities.
| ~ Discussion|| |
AIDS-associated cryptococcal meningitis accounts for 80-90% of all patients with cryptococcosis. Fifteen percent of these meningitis cases may have associated cutaneous lesions. Cutaneous cryptococcal manifestation, a rare but important feature of disseminated cryptococcosis, may precede systemic symptoms by as long as 8 months.  Approximately 85% of patients with cryptococcosis have impaired cell-mediated immunity. However, cutaneous cryptococcal disease usually represents the haematogenous dissemination of cryptococcosis. Its presentation has various clinical morphologies: A draining sinus tract, verrucous nodules, molluscum-like lesions and erythematous, indurated plaques and so on. Yet, none of these manifestations are pathognomic for cryptococcal infection. Confusion with other resembling diseases is not uncommon and disseminated cryptococcosis without treatment has a high mortality rate and appropriate systemic antifungal therapy can significantly improve the outcome. , Although pancytopenia may result from cryptococcosis, there are other more important causes which is given due importance in investigative work-up. If infectious cause is not suspected from additional clinical features with due consideration of the locally prevalent infectious diseases, the chances of missing the diagnosis is high and may lead to case fatality. Manipur, in the north-eastern corner of India is one of the high prevalent states of HIV infection.  It is also an endemic area of penicilliosis marneffei, with multiple cutaneous papules as the main presenting feature.  Considering the previous history of herpes zoster, cutaneous manifestation and weight loss in last 1 month, she was suspected to have cutaneous manifestation of penicilliosis and aspiration cytology was performed. It is important that all patients with pulmonary and extra-pulmonary cryptococcal disease perform a lumbar puncture to rule out concomitant central nervous system (CNS) infection.  However, in this case, lumbar puncture was not done as there was no sign and symptoms of meningeal irritation and patient's reluctance to undergo the procedure. The patient responded well to antifungal therapy. It is the awareness of the locally prevalent infectious diseases in a setting of high HIV prevalence that prompted precise investigative procedures, early diagnosis and successful management of the case.
| ~ Acknowledgement|| |
The first author acknowledges the Department of Biotechnology, Ministry of Science and Technology, Govt of India for providing grant (Grant BT/39/NE/TBP/2010).
| ~ References|| |
Philip KJ, Kaur R, Sangeetha M, Masih K, Singh N, Mani A. Disseminated cryptococcosis presenting with generalized lymphadenopathy. J Cytol 2012;29:200-2.
Yadalla HK, Gandikota RR. Cutaneous cryptococcosis: A marker of life threatening disseminated cryptococcosis in HIV AIDS. Our Dermatol Online 2011;2:203-6.
Mi HB, Seung N, Dongheui A, Mi NK, Sung HK, Ki HP, et al
. Two cases of cryptococcuria developed as isolated cryptococcuria and disseminated cryptococcosis. Korean J Clin Microbiol 2011;14:148-52.
Ranjana K, Priyokumar K, Singh TJ, Gupta ChC, Sharmila L, Singh PN, et al
. Disseminated Penicilliummarneffei
Infection among HIV-Infected Patients in Manipur State, India. J Infect 2002;45:268-71.
Rico MJ, Penneys NS. Cutaneous cryptococcosis resembling molluscum contagiosum in a patient with AIDS. Arch Dermatol 1985;121:901-2.
Visnegarwala F, Graviss EA, Lacke CE, Dural AT, Johnson PC, Atmar RL, et al
. Acute respiratory failure associated with cryptococcosis in patients with AIDS: Analysis of predictive factors.
Clin Infect Dis 1998;27:1231-7.
Shu-Hao C, Jen-Wen H, Shih CC, Lai P. Disseminated cryptococcosis with cutaneous and central nervous system involvement in a diabetic patient. J Intern Med Taiwan 2009;20:187-91.
National AIDS Control Organisation (NACO) HIV sentinel surveillance and HIV estimationin India; 2007.
Singh PN, Ranjana K, Singh YI, Singh KP, Singh SS, Kulachandra M, et al
. Indigenous disseminated Penicillium marneffei
infection in the state of Manipur, India: Report of four autochthonous cases. J Clin Microbiol 1999;37:2699-702.
Saag MS, Graybill RJ, Larsen RA. Practice guidelines for the management of cryptococcal disease. Infectious Diseases Society of America. Clin Infect Dis 2000;30:710-8.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]