CASE REPORT

A case of oral ulceration and disseminated histoplasmosis

in HIV infection
D Sharma*, A McKendry

, S Nageshwaran

and J Cartledge

*Charing Cross Hospital, Imperial College Healthcare NHS Trust;

Mortimer Market Centre;

University College London;

Mortimer Market Centre,
London, UK
Summary: A 51-year-old Malawian woman presented with persistent mouth ulceration and an eight-month history of non-specic
respiratory symptoms. Histoplasma capsulatum was diagnosed on gum, gastric and lymph node biopsies. Identication of
H. capsulatum prompted HIV testing and the patient tested positive with a CD4 count of 40 cells/mm
3
. The diagnosis of
histoplasmosis was delayed due to its unusual presentation.
Keywords: HIV, AIDS, Histoplasma capsulatm, disseminated histoplasmosis, diagnosis, oral ulceration
INTRODUCTION
Oral ulceration is an unusual presentation of disseminated his-
toplasmosis
1,2
particularly in the UK where it has been reported
rarely.
3
It tends to occur in advanced HIV infection.
2
We believe
steroids unmasked the diagnosis in the present case. This case
also highlights the importance of keeping in mind a wide differ-
ential diagnosis, and early HIV testing.
CASE REPORT
A 51-year-old Malawian woman, who had moved to the UK 10
years previously, presented with a 10-day history of cough,
haemoptysis and shortness of breath, following a house re.
The chest X-ray (CXR) demonstrated widespread nodules bilat-
erally. Examination and routine bloods were normal. Sputum
samples were repeatedly acid-fast bacilli negative. Her respirat-
ory symptoms improved and were attributed to smoke inhala-
tion injury.
The CXR abnormalities were followed up with a high-
resolution computed tomography scan of the chest. This
showed multiple small nodules in both lungs (Figure 1). A
raised erythrocyte sedimentation rate of 96 mm/hour, a serum
angiotensin converting enzyme of 92 units/L and persistent
changes on serial CXRs were noted. Broncho-alveolar lavage
showed a lymphocytosis (88%), with no malignant cells.
Transbronchial biopsy showed evidence of patchy chronic
inammation, with no granulomas. Bacterial and fungal cultures
were negative. The differential diagnosis included sarcoidosis
and mycobacterial infection. HIV testing was considered, but
not pursued, as the patient disclosed a negative test six years pre-
viously and denied any subsequent high-risk behaviour.
Sarcoidosis was considered the more likely diagnosis, and
25 mg prednisolone daily was commenced. Two weeks later,
the patient presented with a weeks history of left lower jaw
pain. An ulcer and swelling was seen at the lower left edentu-
lous ridge in the premolar region at the site of a tooth extrac-
tion, which had been performed several months previously. A
subsequent biopsy demonstrated features of Histoplasma capsu-
latum (Figure 2).
This prompted HIV testing, which was positive. Prednisolone
was discontinued and oral itraconazole commenced. The CD4
count was 40 cells/mm
3
and HIV viral load (VL) was 40,000,000
copies/mL. Two weeks after starting itraconazole, the patient
was re-admitted with fevers, mouth ulcers and submandibular
swelling at the site of the recent gumbiopsy. Ultrasound scanning
showed submandibular lymphadenopathy. Fine needle aspira-
tion demonstrated granulomatous inammation. H. capsulatum
was subsequently cultured. Intravenous liposomal amphotericin
B was initiated and the swelling improved.
Ten days after starting liposomal amphotericin B, the patient
had an episode of haematemesis. Gastroscopy demonstrated
four pale duodenal lesions; biopsy showed features of
H. capsulatum consistent with disseminated disease. As the
patient improved, treatment was changed to oral itraconazole.
Anitretroviral therapy was commenced with raltegravir and
tenofovir/emtricitabine, chosen due to their lack of interactions
with itraconazole. Six weeks later, her CD4 count was 230 cells/
mm
3
, and HIV VL ,50 copies/mL. She currently remains
stable as an outpatient and continues on itraconazole mainten-
ance therapy.
DISCUSSION
H. capsulatum var capsulatum is endemic in parts of the USA,
Central and South America and tropical Africa. In Europe,
however, it is rare.
3,4
Its disseminated form is AIDS dening,
the gastrointestinal tract being commonly involved.
2,4
Oral
lesions are unusual, indicative of immunosuppression and fre-
quently of disseminated disease.
1,2
Our patient had few symptoms suggesting disseminated
disease; the oral ulceration worsened with corticosteroids,
which may have unmasked the underlying diagnosis.
5
Histoplasmosis often exhibits clinical features overlapping
with those of tuberculosis and sarcoidosis.
5,6
These may
include fever, malaise, dry cough, night sweats, anorexia and
weight loss, but gastrointestinal symptoms often predominate.
It is important for clinicians practising in low endemicity
areas such as the UK to consider this diagnosis in patients
Correspondence to: D Sharma
Email: davinaosharma@gmail.com
International Journal of STD & AIDS 2012; 23: 522523. DOI: 10.1258/ijsa.2011.011261
with potential previous exposure.
3
Greater emphasis upon the
travel history may have led to earlier diagnosis and treatment.
This case also illustrates that unusual oral lesions often indi-
cate disseminated disease in advanced HIV infection. Biopsy
should be considered early, as culturing H. capsulatum is con-
sidered the gold standard diagnostic test.
4,7
Where dissemi-
nated disease is suspected, bone marrow trephine and culture
are recommended. Histoplasma antigen testing was not done
here, but is recommended both in diagnosis and disease moni-
toring, where available. Itraconazole is recommended for treat-
ment of mild-to-moderate disseminated disease, amphotericin
B being reserved for moderate-to-severe disease.
7
Finally, our patient was diagnosed HIV-positive eight
months after her initial presentation. This case illustrates the
importance of HIV testing of all acute admissions in the UK
where prevalence exceeds 2/1000, as per the British HIV
Association and National Institute for Health and Clinical
Excellence guidance;
8,9
consideration should be given to retest-
ing patients from high-risk areas, even in the absence of recent
HIV risk behaviour.
ACKNOWLEDGEMENTS
Professor Rob Miller and Dr Magali Taylor, University College Hospital, London;
Dr Selvam Thavaraj, Guys Hospital, London; Chris Sproat, Kings College
London, UK.
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(Accepted 11 December 2011)
Figure 1 Computed tomography scan of the chest showing mul-
tiple small modular opacities in both lungs
Figure 2 Histological appearance: (a) medium-power photomicrographic
view of the subepithelial tissue demonstrating replacement of the lamina
propria by a diffuse inltrate comprising predominantly sheets of macro-
phages with plasma cells and neutrophil polymorphs towards the top
right (Haematoxylin and eosin, scale bar = 100 mm). (b) and (c) high-
power photomicrographic view demonstrating intra-cytoplasmic particles
consistent with histoplasma species. Note the peripheral nuclear conden-
sation in (b) periodic acid-Schiff with diastase digestion, (c) Gomori-
Grocott methanamine silver, scale bar = 50 mm)
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Sharma et al. Oral ulceration and disseminated histoplasmosis in HIV infection 523
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