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Corresponding author: Makoto Hasegawa, Department of General Internal Medicine, Fujita Helth University Okazaki Medical Center, 1 Harisaki, Okazaki-city, Aichi-prefecture, Japan, Phone No: +81-564-64-8800.
We present the case of a HIV-positive, antiretroviral therapy–naïve patient with extrapulmonary pneumocystosis.
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The splenic mass reduced in size with drainage, and the other masses resisted interventions.
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Early antiretroviral therapy served as a successful treatment strategy.
Abstract
Pneumocystis jirovecii is a common opportunistic fungal pathogen that commonly affects immunocompromised individuals and can cause P. jirovecii pneumonia. Extrapulmonary P. jirovecii infections are extremely rare. Herein, we present a case of an HIV-positive, antiretroviral therapy–naïve patient who had extrapulmonary pneumocystosis (EPC). He presented with complaints of decreased appetite, abdominal fullness, and weight loss. Computed tomography (CT) revealed multiple low-attenuation masses in the spleen, liver, and both adrenal glands but no pulmonary involvement. A core-needle biopsy of a splenic lesion confirmed the diagnosis of EPC. The patient was initiated on intravenous trimethoprim-sulfamethoxazole (TMP-SMX) and CT–guided percutaneous catheter drainage of the splenic lesion was performed. Intravenous TMP-SMX therapy was completed in 3 weeks and intravenous pentamidine (250 mg daily) therapy was commenced. Pentamidine was completed after 3 weeks, and antiretroviral treatment (ART) was initiated with dolutegravir 50 mg and Descovy HT (emtricitabine [200 mg] and tenofovir alafenamide fumarate [25 mg]). After starting ART, the patient's clinical condition improved, and the abscesses gradually reduced. TMP-SMX is commonly used to treat EPC; however, there is no standard method of treatment. ART may become the key to EPC treatment in individuals with HIV infection.
Pneumocystis jirovecii (P. jirovecii) is a common opportunistic fungal pathogen mostly affecting immunocompromised individuals; it usually presents as a pulmonary infection. The incidence of P. jirovecii pneumonia (PJP) markedly decreased in response to antiretroviral therapy (ART) and the adoption of the general recommendations for PJP prophylaxis (
Conversely, extrapulmonary pneumocystosis (EPC) is an extremely rare disease with a high mortality rate. This mostly occurs in patients with HIV with a minimal systemic distribution of aerosolized pentamidine prophylaxis or those with advanced HIV infection without prophylaxis, even without pulmonary involvement. With the recent widespread use of antiretroviral treatment (ART) and prophylaxis, the incidence has decreased dramatically. Herein, we present a case of an ART-naïve patient with HIV who developed EPC with no pulmonary involvement.
Case
A 39-year-old homosexual man without medical history was admitted with complaints of a decreased appetite, abdominal fullness, and an unintentional weight loss of nearly 8 kg over the past year. He was evaluated in a primary care hospital and found to have anemia. Abdominal ultrasound showed a hypoechoic splenic lesion. He was referred to our facility for further evaluation.
On admission, the patient was afebrile and alert with normal vital signs. Physical examination revealed a nontender, palpable mass in the epigastric region with a diameter of approximately 15 cm. Laboratory test results were notable for elevated C-reactive protein (5.8 mg/L) and anemia (hemoglobin concentration, 11.5 g/dL). There were no other abnormal data (hematocrit, 35.7%; platelets, 223 000/mm3; white blood cell count, 5200/mm3 with 53.0% neutrophils, 26.8% lymphocytes, and 7.8% monocytes; serum electrolytes, blood urea nitrogen, amylase, lipase, liver enzymes, and serum bilirubin levels were within normal limits).
A computed tomography (CT) scan revealed multiple low-attenuation masses with thick calcified rims in the spleen, liver, and bilateral adrenal glands (Figure 1). A core-needle biopsy of a splenic lesion aspirated 400 mL of a serous, brown fluid.
Figure 1Day 1. On the first day after hospitalization, a computed tomography (CT) scan demonstrated multiple low-attenuation masses with thick calcified rims in the spleen, liver, and bilateral adrenal glands. Day 38. CT after 3 weeks of intravenous trimethoprim-sulfamethoxazole therapy and CT-guided percutaneous catheter drainage of the splenic lesion with current intravenous pentamidine therapy, the maximal spleen abscess size was reduced. However, the sizes of the other abscesses did not change. Day 294. After the initiation of antiretroviral therapy, the viral load of the human immunodeficiency virus decreased, and CD4 increased. All abscess sizes had gradually reduced.
Pathological examination of the aspirate revealed granulomatous inflammation with necrotic cells and calcification. Grocott's methenamine silver stain revealed many interspersing, round, black pneumocystis cyst-like cells. The polymerase chain reaction was positive for P. jirovecii. Gram stain, acid-fast stain, and bacterial and mycobacterial cultures were all negative. A diagnosis of EPC involving the spleen, liver, and adrenal glands, but not the lungs, was established. Further workup revealed that he was seropositive for HIV with a CD4 count of 36.3 cells/mL and an HIV RNA level of 8.0 × 105 copies/mL.
On day 1 after hospitalization, the patient was started on intravenous trimethoprim-sulfamethoxazole (TMP-SMX), and CT-guided percutaneous catheter drainage of the splenic lesion was performed. The maximal splenic abscess subsequently appeared reduced on CT (Figure 1); however, the other abscesses did not change.
After completion of intravenous TMP-SMX in 3 weeks, on day 24, intravenous pentamidine (250 mg daily) therapy was initiated. As the splenic abscess had reduced and waste fluid was absent, we removed the drainage tube 33 days after insertion. The other abscesses were yet to diminish.
We decided to discontinue intravenous pentamidine after 3 weeks and start ART with careful observation. On day 43, we administered dolutegravir 50 mg and Descovy HT (emtricitabine [200 mg] and tenofovir alafenamide fumarate [25 mg]) and introduced a PJP prophylactic regimen with TMP-SMX (1 single-strength tablet daily). With ART, the CD4 count increased, and the HIV viral load decreased. On day 133, the CD4 count had increased to 108.5 cells /mm3, and HIV RNA became undetectable. On day 294, the CD4 count had increased to 236.6 cells /mm3, but HIV RNA remained undetectable. The patient's condition improved, and he was discharged. The abscesses gradually reduced in size (Figure 1); at the most recent follow-up, 2 years later, no relapse is noted.
Discussion
The overall incidence of EPC among individuals with HIV is estimated to be 0.06%–2.5% (
). It has a high mortality rate and occurs mostly in patients with HIV with a minimal systemic distribution of aerosolized pentamidine prophylaxis or with advanced HIV infection without prophylaxis, even without pulmonary involvement (
The pathogenesis of extrapulmonary infections is unclear. It probably is associated with hematogenous or lymphatic dissemination from the lung. It can affect most organs; lymph nodes, spleen, liver, and bone marrow are most commonly infected (
). With the widespread use of ART and prophylaxis, the incidence has decreased dramatically.
We describe a patient with AIDS with the uncommon feature of EPC presenting as multiple intra-abdominal abscesses without pulmonary disease. Generally, the differential diagnosis of intra-abdominal masses in patients with HIV includes bacterial, mycobacterial, or fungal infection, lymphoproliferative disorder, Kaposi's sarcoma, or smooth-muscle tumors. On abdominal CT, such lesions present as lymph node enlargement, hepatomegaly or splenomegaly, gastrointestinal mass or wall thickening, and low-attenuation lesions in the liver or spleen (
). A report described a patient with AIDS with hepatic and splenic pneumocystosis failing to resolve after 2 months of daily therapy with intravenous TMP-SMX, yet subsequently had a clinical, radiologic, and biologic response after 3 weeks of intravenous pentamidine therapy (
). Furthermore, there is a suggestion that P. jirovecii in infections of extrapulmonary sites might be different from pneumonia-causing strains, and these may be resistant to TMP-SMX (
In this case, intravenous pentamidine was ineffective, as indicated by the lack of improvement according to images. We suspect that the antimicrobial agent was insufficient because of the disease severity or the limited distribution of the medicine. After starting ART, the intra-abdominal abscesses gradually diminished in size. This clinical course suggests that early ART induction, similar to that in PJP, may be the key to EPC treatment. There is a consensus for early ART initiation for PJP, preferably as soon as patients are stable on PJP treatment (
Centers for Disease Control and Prevention (CDC); National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.
Exacerbation of the splenic abscess related to immune reconstitution inflammatory syndrome (IRIS) after introducing ART was a concern. In patients with PJP, IRIS is infrequent after ART initiation (
), but it is unknown if this is the case in patients with EPC. If IRIS occurs, there is a risk of splenic abscess rupture, which could be fatal. Splenectomy is a possible treatment modality for patients with EPC who are nonresponsive to medical therapy and at risk of rupture (
). Percutaneous drainage is an alternative for critically ill patients and young patients where vigorous attempts are made to preserve the spleen, and the abscess is the unilocular or bilocular case (
In this case, abscess drainage was useful for maximal splenic abscess control and reduced rupture risk. We could start ART without the risk of splenic rupture. Early ART initiation while undertaking drainage should be considered in patients with EPC with large abscesses.
To the best of our knowledge, there are no other reports of ART-naïve HIV-positive patients with EPC showing improvement with early ART induction. However, this may become the key to EPC treatment.
Conflict of Interest
None declared.
Funding Sources
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
Centers for Disease Control and Prevention (CDC); National Institutes of Health; HIV Medicine Association of the Infectious Diseases Society of America. Guidelines for prevention and treatment of opportunistic infections in HIV-infected adults and adolescents: recommendations from CDC, the National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America.
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