ID Ground Rounds — Stanford University: Male, 46, HIV Patient with Fever and Dyspnea
ABSTRACT & COMMENTARY
ID Ground Rounds — Stanford University: Male, 46, HIV Patient with Fever and Dyspnea
By Carlos A. Gomez, MD
Infectious Diseases Fellow, Stanford University Hospital
Dr. Gomez reports no financial relationships in this field of study
Case History
A 46-year-old man was admitted to our hospital due to progressive dyspnea, non-productive cough and fever. Two months prior to admission, he started to develop sustained weight loss and dyspnea associated with exertion. Ten-days prior to his presentation, dyspnea progressed to minimal exertion significantly limiting his functional status. He also developed fever (38.3°C), non-productive cough and dysphagia. He sought care at a local Emergency Department and was discharged the same day with steroid inhalers, oral fluconazole for thrush and a 3-day course of prednisone. He was admitted to our institution 5 days later due to worsening of respiratory symptoms. At admission, he denied pleurisy, dysuria, diarrhea, focal neurological deficits, headaches or vision disturbances.
HIV history
The patient was diagnosed with HIV infection in 1986 but first developed AIDS in 1994 when he was found to have pulmonary Mycobacterium Avium complex (MAC) infection and chronic diarrhea. He was started on antiretroviral therapy (ARV) and appropriate antimicrobial prophylaxis with adequate immunological recovery. Unfortunately, the patient abandoned ARV therapy in mid-2008 at a time when his CD4+ T cell count was 450 cells/mm3. Besides HIV infection, his past medical history was unremarkable. There was no history of other sexually transmitted disease. He had developed disseminated skin rash after trimethoprim-sulfamethoxazole exposure. He quit smoking 5-year prior presentation and denied IV drug use. He had often traveled throughout the Central Valley of California but there was no history of other recent domestic or international travel nor of contacts with ill individuals. He had no history of opportunistic infections other than those previously mentioned.
Physical Examination
On physical examination, he looked cachectic and chronically ill but not in respiratory distress. His temperature was 38.7°C, blood pressure was 106/66 mmHg, heart rate was 97 beats per minute, respiratory rate was 30 breaths per minute. His oxygen saturation was 95% at 0.5 L/min of oxygen by nasal cannula. Oral mucosa inspection revealed thrush. Left greater than right basilar inspiratory crackles were noted. Otherwise, his examination was unremarkable.
Lab test and Imaging
Laboratory investigation revealed a normal WBC (8100, 72% neutrophils); hemoglobin and platelets counts were also within normal levels. His creatinine was 1.1 mg/dL. Liver tests were normal. His urinalysis showed no pyuria. Arterial blood gases showed a pH of 7.46 and PaO2 146, with a normal calculated A-a gradient; LDH 287 U/L, CD4+ cell count: 12 cells/mm,3 HIV viral load 133.000 copies. Blood cultures, pneumococcal urine antigen and legionella urine antigen were each negative. Initial chest X-ray showed diffuse bilateral ground-glass opacities in the left lower lobe. A non-contrast CT of the chest showed multilobar ground-glass opacities which were more coalescent in the left lower lobe.
Clinical course
The patient was admitted to a medical ward and treatment was started with IV ceftriaxone and azithromycin for presumed community acquired pneumonia. After 48 hours, his oxygen requirements increased to 3 L/min in order to keep his oxygen saturation above 90%. He remained febrile with no significant clinical improvement. Microscopy of a sputum specimen obtained by induction showed > 10 epithelial cells, and a negative Gram stain. Direct Fluorescent Antibody (DFA) staining for Pneumocystis was negative. Blood cultures and a respiratory viral panel from nasopharyngeal swab were negative. A serum ß-D-Glucan (Fungitell test) was positive at 129 pg/mL (cutoff ≥ 80 pg/mL). On Day 3 of hospital stay, before the ß-D-Glucan test was reported, he underwent bronchoscopy with bronchoalveolar lavage (BAL). DFA for PCP performed on a BAL specimen was positive and treatment with atovaquone 750mg BID was instituted. The patient failed TMP-SMX desensitization due to development of skin rash and lip edema. Unfortunately, despite multidisciplinary efforts the patient declined ARV therapy and was discharged on atovaquone which was to be continued for prophylaxis against recurrence of PCP.
Discussion
Pneumocystis jiroveci, the etiologic agent of human pneumocystis pneumonia (still referred as PCP) remains an important opportunistic agent in HIV-patients who remain unaware of their diagnosis and those with CD4+ count ≤ 200 cells/mm3 in the absence of adequate PCP prophylaxis.1 Since the introduction of TMP-SMX as an effective PCP prophylaxis strategy in 1989 and the subsequent advent of highly active antiretroviral therapy (HAART) in 1996, the incidence of PCP in HIV population has markedly and sustainably declined. PCP should be suspected in the appropriate host presenting with the triad of resting or exertional dyspnea, fever and non-productive cough. Hypoxemia is the cardinal manifestation of PCP; oxygen desaturation following mild exertion is often abnormal and might be used to identify patients at early disease stages, including the 10% with no abnormalities observed on chest X-ray. Extrapulmonary manifestations of PCP are very rare but instances of involvement of lymphoid-tissues, bone marrow, spleen, GI tract, ocular, and thyroid gland have been reported. The most common radiographic pattern in chest radiographs is diffuse, bilateral, symmetrical reticulo-nodular infiltrates, which correlates with ground-glass opacities found in CT.2 Pleural effusion, consolidation, mediastinal adenopathy and cavitation are uncommon in the absence of other pulmonary pathogens. The presence of spontaneous pneumothorax in an HIV-patient should raise the suspicion for PCP2. Of note, the presence of oro-pharyngeal candidiasis has historically been associated with high risk of PCP and its presence alone, is an indication for PCP prophylaxis.
The suspicion of PCP raises a diagnostic dilemma for the clinician. Due to the inability to culture the organism, a microbiological diagnosis relies on the visualization of the organism in respiratory secretions. Induced sputum with the use of various stains techniques (e.g. Direct Fluorescent Antibody, Grocott-Gomori’s methenamine silver, and Giemsa stain) has reported a wide range of sensitivity (60-95%).1,3 In experienced centers, DFA staining in induced sputum has demonstrated a sensitivity as high as 90% when compared with DFA in BAL samples. The above implies the availability of fluorescent microscopy, laboratory expertise, and a standardized protocol that includes motivated and highly trained respiratory therapy personnel to guarantee lower respiratory tract sampling. As these conditions are not available everywhere, the availability of a PCP-specific serum marker has been highly desirable. (1-3)-ß-D-glucan (ß-glucan), is a component of many fungi wall, including P. Jirovecii, and has emerged as a potential diagnostic tool in HIV-patients with possible PCP. When a cutoff value of ≥ 80 pg/mL was used in HIV-patients with suggestive respiratory symptoms, the sensitivity of the ß-glucan test was 92.8% and its specificity 75%.4 False positive results may occur in patients treated receiving piperacillin/tazobactam or in the presence of systemic infections due to other fungi, such as invasive aspergillosis and histoplasmosis. Remarkably, mucosal candidiasis was not statistically significant associated with elevated ß-glucan serum levels.4 Polymerase chain reaction (PCR) is an emerging method for PCP diagnosis with a high sensitivity, but its inability to distinguish true infection versus mere colonization is problematic. The potential role of quantitative PCR and its integration in PCP-diagnostic algorithms is under study.
A strong suspicion of PCP should trigger the timely initiation of therapy for this infection. TMP-SMX remains the treatment of choice for PCP and should be preferred over other alternative options (e.g. primaquine/clindamycin, dapsone/trimethoprim (in the absence of G6PD deficiency), atovaquone or IV pentamidine). Cases of severe PCP, defined as the presence of PaO2 <70 mmHg while breathing ambient air or an alveolar-arterial O2 gradient ≥35 mmHg, require the use of adjunctive corticosteroid therapy. In contrast to the findings in this patient, the gas exchange abnormalities are usually greatly out of proportion to the radiographic findings. In this case, the use of prednisone prior to the current admission may have blunted the pulmonary inflammatory response leading to the normal oxygenation observed at the initial presentation.
Diagnosis: Pneumocystis jiroveci pneumonia.
REFERENCES
- Kovacs JA, et al. New insights into transmission, diagnosis, and drug treatment of Pneumocystis carinii pneumonia. JAMA 2001;286(19):2450-2460.
- DeLorenzo LJ, et al. Roentgenographic patterns of Pneumocystis carinii pneumonia in 104 patients with AIDS. Chest 1987;91(3):323-327.
- Turner D, et al. Induced sputum for diagnosing Pneumocystis carinii pneumonia in HIV patients: nNw data, new issues. Eur Respir J 2003;21(2):204-208.
- Wood BR, et al. Test performance of blood beta-glucan for Pneumocystis jirovecii pneumonia in patients with AIDS and respiratory symptoms. AIDS 2013;27(6):967-972.
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