Extrapulmonary Pneumocystis jirovecii infection in an advanced HIV ... - BMC Infectious Diseases

Pneumocystis jirovecii pneumonia (PCP) develops mainly in patients with advanced HIV infection, newly diagnosed patients, and those not using antiretroviral therapy (ART). Dry cough, subacute fever, dyspnea, desaturation, and interstitial infiltration with ground glass opacity from chest imaging are presenting signs and symptoms that increase the suspicion of a diagnosis of PCP. Extrapulmonary pneumocystosis (EPCP) is an extremely rare condition [5] after the wide availability use of ART. Approximately 50–80% of reported EPCP occurred in advanced HIV-infected patients who did not receive TMP/SMX prophylaxis or received aerosolized pentamidine as prophylaxis [6]. EPCP was also reported in other types of immunocompromised patients such as patient with connective tissue disease, solid organ transplant or hematopoietic stem cell transplant recipients and those with hematologic malignancy who receive immunosuppressive drugs [6, 7]. In this article, we describe the second reported case of an advanced HIV patient with EPCP presenting as a paravertebral mass [8]. Our patient was diagnosed EPCP while taking a high dose of prednisolone and a double strength of TMP/SMX three times per week for PCP prophylaxis. However, this does not imply that TMP/SMX prophylaxis is ineffective because paravertebral soft tissue mass was already found on CT scan of the whole abdomen while starting TMP/SMX prophylaxis.

The incidence of EPCP among HIV-infected patients was estimated to be 0.06–2.5% [7]. The clinical presentation of EPCP depends on the organ(s) involved, and can present with or without coexisting pulmonary infection [6, 7]. Approximately 60–64% of patients with EPCP had multiple organ involvement at either contiguous or non-contiguous sites. Postmortem evidence revealed the routes of dissemination to be hematogenous, lymphatic, or direct spreading from an adjacent organ [6, 9]. From 1954 to 1997, there were 90 and 16 cases of EPCP reported in HIV-infected and non-HIV-infected patients, respectively. Among HIV-infected patients, EPCP was the most prevalent in advanced disease and more frequently presented with multiple organ involvement. Ocular or ear was the most common organ involved in those with single organ involvement and was associated with a better prognosis [6]. In contrast, non-HIV-infected patients with EPCP had non-specific symptom(s), more dissemination, and had worse outcome with > 50% diagnosed postmortem. Other common organs involved include the lymph nodes, spleen, liver, and bone marrow. Less commonly involved organs include the pleura, trachea, diaphragm, meninges, cerebral cortex, gastrointestinal tract, pancreas, kidney, heart, adrenal gland, pituitary gland, parathyroid gland, and spine [6]. Although more than 100 cases of EPCP were reported before 1997, only 5 cases of adult EPCP were reported after that time point and all 5 of those patients were HIV positive [8, 10,11,12,13]. Of those 5 patients, 3 were treatment-naïve with a CD4 count of less than 50 cells/mm³ [8, 10, 12], and 4 out of 5 had multiple organ involvement. One of those 3 treatment-naïve cases had paravertebral soft tissue involvement like the patient described in the present report [8]. Only one patient who was on ART, with a CD4 count of 180 cells/mm³ had EPCP restricted to only the ear [11] (Table 1).

Table 1 The demographic and clinical characteristics of 5 HIV-infected patients who developed extrapulmonary Pneumocystis jirovecii infection and that had their cases reported after 1997

Full size table

A diagnosis of EPCP can be established via demonstration of the eosinophilic foamy exudates in which P. jirovecii cystic form (ascus) or trophic form are embedded in affected tissue by Gomori methenamine silver (GMS) staining or periodic acid-Schiff (PAS) staining. The finding of GMS staining with spherical, helmet, or crescent non-budding ascus cyst-like structure, approximately 4–8 μm in size differs from Histoplasma spp. which described as oval budding yeast with smaller in sizes of 1–4 μm [14]. Notably, a diagnosis of EPCP can be delayed due to uncommon presentation of EPCP and delayed HIV diagnosis, such as in our case, which was referred for investigation of a paraspinal mass before our patient's HIV status was investigated. Detection of P. jirovecii in a pulmonary specimen, such as BAL fluid or lung biopsy, with Giemsa or immunofluorescent stains is also useful when considering EPCP in the differential diagnosis. Histopathologic examination with GMS staining is generally sufficient for detection of P. jirovecii; however, detection of P. jirovecii by PCR, which is more sensitive than GMS staining, may be useful to confirm the diagnosis, especially in EPCP patients who present with uncommon manifestation. However, BAL fluid PCR was negative for P. jirovecii in our patient. It could probably be explained by several reasons. First, our patient received the prophylaxis dose of TMP/SMX for 3 months before performing bronchoscopy, which might have cleared P. jirovecii DNA, resulting in false negative BAL fluid PCR [15, 16]. In addition, the BAL specimen was sent for PCR testing after the IFA for P. jirovecii yielded a negative result, which means that the specimen might not properly preserved for DNA testing.

There is currently no specific recommendation for the treatment of EPCP. Previous EPCP cases among HIV-infected patients were treated with TMP/SMX as the first-line regimen for PCP [10]. Approximately 80% of EPCP cases series were treated with TMP/SMX. Other drugs, such as dapsone plus trimethoprim, primaquine plus clindamycin, atovaquone, or intravenous pentamidine have been used when patients could not tolerate or did not improve after treatment with TMP/SMX [6]. The duration of treatment varied from 3 to 4 weeks [8, 11, 12]; however, prolonged duration of antibiotics with surgical drainage would be needed in cases of large and multiple intra-abdominal organ abscesses [10]. The prognosis is poor with > 50% mortality among those with multiple organ involvement [6]. Early initiation of effective ART is important for restoring immune status in HIV-infected patients. Our patient had clinical improvement after treatment with 3 weeks of TMP/SMX and early ART initiation.

In conclusion, EPCP has become an extremely rare disease in HIV-infected patients after the widespread use of ART. EPCP should be considered in ART-naive HIV-infected patients who are suspected of having or diagnosed with PCP and in patients with atypical symptoms and/or signs. Histopathologic examination with GMS staining of affected tissue is necessary for the diagnosis of EPCP.

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