CASE REPORT JIACM 2005; 6(4): 327-30
* Senior Resident, ** Professor, Department of Medicine, *** Additional Professor, Department of Pathology,
All India Institute of Medical Sciences, Ansari Nagar, New Delhi - 110 029.
Disseminated Histoplasmosis –
Fulminant Presentation in an AIDS Patient
Amit Kumar Dutta*, Rita Sood**, AK Karak***
Abstract
We present here the report of a patient who initially presented as prolonged fever, bicytopenia and granuloma in the bone marro
and was later found to be HIV positive.
Introduction
Extra-pulmonary histoplasmosis usually presents with
unexplained fever and weight loss, but in some, especially
with high antigenic load, it may present as a syndrome
resembling sepsis1. Here we report one such case where
AIDS was not diagnosed initially.
Case report
A 43-year-old male patient presented with moderate
grade intermittent fever with evening rise for past six
weeks. He was anorexic and had lost significant weight.
He was a chronic smoker and denied history of blood
transfusion or high risk behavior for HIV infection. On
examination, he was pale and febrile (101º F). The rest of
the general physical examination was normal. There was
mild, firm, non-tender splenomegaly. The examination of
cardiovascular, respiratory, and neurological system was
unremarkable.
Laboratory evaluation showed haemoglobin of 7.4 g/dL;
platelets - 2,63,000/mm3; TLC - 3,900/mm3; DLC - N72L25E2;
ESR- 55 mm in the first hour by Westergren’s method.
Biochemical and microbiological evaluation was normal.
Chest X-ray was unremarkable. Ultrasonography of the
abdomen showed mild splenomegaly with no focal
lesions.
Bone marrow aspirate was normocellular and showed no
parasites. Bone marrow biopsy showed non-necrotising
epithelioid cell granuloma with Langhans giant cells
(Figure 1). No acid-fast bacilli were seen. Serum
angiotensin-converting enzyme (ACE) level was within
normal limits. Considering tuberculosis as the commonest
cause of fever of unknown origin (FUO) in India2 and
presence of granuloma in bone marrow, this patient was
started on anti-tuberculous treatment (ATT). Few days
later, patient developed a plaque on neck, the biopsy of
which showed features suggestive of photosensitive
lichenoid eruption. He showed initial subjective
improvement of symptoms on ATT.
However, our patient followed-up four weeks later with
the complaint of persistence of fever. A repeat
examination showed bilateral axillary and cervical
lymphadenopathy. Right cervical lymph node was
biopsied. X-ray chest at this time revealed bilateral miliary
shadows and patient was advised re-admission which he
declined. Liver function tests performed at this stage were
normal. He was continued on ATT. Contrast enhanced
computed tomography (CECT) of chest and abdomen was
performed. It showed bilateral miliary lung lesions, some
of which had coalesced to form larger opacities. Left para-
aortic lymph nodes were enlarged. Over the next one
week, the patient’s condition worsened and he was
hospitalised with acute lower gastrointestinal bleed. On
examination, he was drowsy, tachypnoeic, hypotensive,
and had marked pallor. Lymph node biopsy report was
received which showed features suggestive of
histoplasmosis with extremely high organism load
(Figures 2A and 2B). An ELISA test for HIV was performed.
Laboratory evaluation at this stage showed haemoglobin
- 6.7 g/dl; platelets - 29,000/mm3; TLC - 12,100/mm3; DLC -
N68L28E1; total bilirubin/direct was 4.4/2.6 mg/dl; total
protein - 5.3 g/dl; Albumin - 1.6g/dl; SGOT/SGPT/SAP -
1,213/119/479 IU/l respectively; prothrombin time was
prolonged(13/25 seconds). X-ray chest showed marked
328 Journal, Indian Academy of Clinical Medicine  circle6  Vol. 6, No. 4  circle6  October-December, 2005
increase in infiltrates in both the lung fields.
Patient was started on IV amphotericin B. Despite blood
transfusion and supportive treatment, his condition
deteriorated and he succumbed to his illness within 12
hours of this admission. The previous skin and bone
marrow biopsies were reviewed and they did not show
presence of fungus. The report of ELISA for HIV was found
to be positive. A final diagnosis of AIDS with disseminated
histoplasmosis was made.
Discussion
Infection with Histoplasma is asymptomatic in 95% of
cases. In immunocompetent patients it usually manifests
as self-limited respiratory infection comprising of fever,
malaise, cough, and chest pain. Chest radiograph may
show focal infiltrates and hilar or mediastinal adenopathy.
In immunocompromised patients, chest radiograph may
show miliary infiltrates which may resemble Mycobacterial
or  Pneumocystis carinii infection. Sometimes the
disseminated infection in such patients can present with
prolonged fever, weight loss, mucocutaneous lesions,
hepatosplenomegaly, lymphadenopathy, pneumonia,
adrenal insufficiency, occasional intestinal ulcerative lesion
and in some with sepsis like illness. Almost all cases of
histoplasmosis in patients with AIDS have been of
disseminated type1.
Histoplasmosis as a cause of fever of unknown origin is
uncommon in India where tuberculosis, especially extra-
pulmonary tuberculosis, is the leading cause in most
series2. Extra-pulmonary tuberculosis accounted for 45%
of cases in a series of 60 FUO patients from this institute3.
In developing countries, tuberculosis is the commonest
cause of granuloma formation and with suggestive clinical
presentation, even in the absence of acid fast bacilli,
Fig. 1: Section from the bone marrow trephine revealing the presence of non-necrotising epithelioid cell granuloma without any organis
and E, x 40).
Journal, Indian Academy of Clinical Medicine  circle6  Vol. 6, No. 4  circle6  October-December, 2005 329
patients are often started on ATT. In this patient, the initial
presentation with low grade fever and weight loss,
absence of history of high risk behaviour for acquiring HIV
infection and blood transfusion, and finding of granuloma
in bone marrow biopsy led to a presumptive diagnosis of
tuberculosis. The appearance of miliary shadows on chest
radiograph might have only strengthened this diagnosis,
but for the fact that the patient worsened clinically while
on ATT. The appearance of lymph node enlargement and
its biopsy led us to the diagnosis of disseminated
histoplasmosis. However, by this time the patient
deteriorated rather acutely and succumbed to his illness.
There are important lessons to be learnt from this case.
Diagnostic efforts should not cease with detection of
granuloma which could be due to different aetiologies
(though in India, tuberculosis is the commonest cause),
and further diagnostic steps should be taken to confirm
the cause of granuloma. Granulomas in bone marrow can
be seen in upto 8% of patients with disseminated
histoplasmosis in AIDS1. In one report from Guatemala (in
Central America), of the 8 patients who had disseminated
histoplasmosis with AIDS, diagnosed over a 10 year period,
all were initially admitted with diagnosis of tuberculosis
with AIDS4. Extra-pulmonary tuberculosis masking
disseminated histoplasmosis has been reported and thus
even if tuberculosis is confirmed, possibility of other
concurrent infection should be kept in mind5. Fungal
infections as a cause of granuloma are usually considered
in differential diagnosis of tuberculosis in patients who
are immunocompromised. Since in this patient HIV was
not suspected on clinical grounds, this differential
diagnosis was not entertained.
We also conclude that a serology for HIV must be
performed in all patients with unexplained fever
Fig. 2A: Section from the lymph node with numberous intra-cellular
histoplasma (arrows) inside macrophages (H and E, x 40).
Fig. 2B: Silver-methenamine stain highlighting the morphology
(arrow) of the fungus (x 40).
irrespective of the presence or absence of high risk
behaviour. This will allow early diagnosis of opportunistic
infections (by increasing the index of suspicion),
appropriate therapeutic intervention and improve
outcome. Also, in patients with AIDS, multiple
opportunistic infections should be kept in mind even if
clinical features point to a single aetiology. Studies are
needed to determine the risk factors, natural history and
develop more rapid and accurate tests for diagnosing
disseminated histoplasmosis.
References
1. Wheat LJ, Connolly-Stringfield PA, Baker RL et al.
Disseminated histoplasmosis in the acquired immune
deficiency syndrome: Clinical findings,diagnosis and
treatment and review of literature. Medicine (Baltimore)
1990; 69: 361-74.
2. Sharma BK, Verma SC et al. Prolonged undiagnosed fever
in northern India. Trop Geogr Medicine 1992; 44 (1-2): 32.
3. Sood R, Aggarwal V, Mukhopadhyay S.Tuberculous
mediastinal adenopathy presenting as fever of unknown
origin. Lancet 1997; 350 (9093):1782.
4. Segura L, Rojas M, Pelaez N et al. Disseminated
histoplasmosis and human immunodeficiency virus type
1 infection : risk factors in Guatemala. Clin Infect Dis 1997;
25: 343-4.
5. Greene L, Peters B, Lucas S B, Pozniak AL. Extra-pulmonary
tuberculosis masking disseminated histoplasmosis in AIDS.
Sex Transm Infect 2000; 76: 54-6.
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