Unusual aetiology of respiratory compromise in a patient with AIDS

Abstract

A 36-year-old African American man with no medical history presented with a recent history of cough and dyspnoea. Initial chest imaging revealed diffuse bilateral lung infiltrates. A subsequent HIV test resulted positive, and he was presumptively diagnosed with AIDS, later confirmed by a CD4 of 88 cells/mm³. Empiric therapy with trimethoprim–sulfamethoxazole was initiated for presumed Pneumocystis jirovecii pneumonia. The patient’s clinical status deteriorated despite treatment. Further workup with chest CT, bronchoscopy and skin biopsy led to a diagnosis of Kaposi sarcoma with pulmonary involvement. Highly active antiretroviral therapy therapy was initiated, along with plans to start chemotherapy. However, the patient’s clinical status rapidly declined, leading to respiratory failure and eventual death. This case underlines the importance of maintaining a broad differential in immunocompromised patients presenting with respiratory symptoms.

Background

Patients with HIV infection develop AIDS when their CD4 count decreases below 200 cell/mm³, rendering them susceptible to opportunistic infections.¹ Given the atypical presentations of respiratory illness in patients with HIV/AIDS, a broad differential diagnosis with a comprehensive workup is warranted. Pulmonary Kaposi sarcoma (KS) is a rare opportunistic disease that may not be considered initially but should be suspected when common etiologies are ruled out. Often overlooked due to its similar presentation with other opportunistic infections, it is a potentially deadly disease if left untreated. Mucocutaneous KS, however, is a more detectible manifestation and less likely to be missed, allowing for prompt diagnosis and treatment initiation. The diagnosis of pulmonary KS is made by correlating the characteristic clinical findings, imaging studies, bronchoscopy and pathology in an immunocompromised patient.²

Case presentation

A 36-year-old African American man with no medical history presented with a 3-week history of dyspnoea and cough that recently became productive of blood-tinged sputum. Social history revealed that he was homosexually active with intermittent condom use. He denied any recent travel, intravenous drug use or taking any medications. On physical examination, the patient was noted to be cachectic in appearance, short of breath requiring supplemental oxygen therapy, with auscultatory chest findings significant for diffuse bilateral rhonchi. A limited skin exam on this admission did not reveal any suspicious skin lesions. Initial chest radiography revealed typical appearing bilateral infiltrates (figure 1) concerning for Pneumocystis jirovecii pneumonia (PJP). An HIV test resulted positive, and he was presumptively diagnosed with AIDS. The patient was started on empiric treatment for PJP with trimethoprim–sulfamethoxazole (TMP–SMX). Follow-up CD4 count resulted in 88 cells/mm³, confirming a diagnosis of stage 3/AIDS. Bronchoscopy with cultures yielded negative results and demonstrated ill-defined, diffuse endobronchial erythema with no suspicious lesions, although it was unsatisfactory due to profuse intraop coughing. As the patient initially responded with clinical improvement on antibiotic therapy, he was presumably diagnosed with PJP and discharged with TMP–SMX and outpatient follow-up to initiate highly active antiretroviral therapy (HAART) therapy. The patient failed to keep the follow-up appointment with the infectious disease clinic.

Figure 1.

Chest X-ray with bilateral infiltrates initially suspicious of Pneumocystis Jirovecii Pneumonia.

Three weeks later, the patient was readmitted with worsening respiratory symptoms despite reported outpatient compliance with TMP–SMX. HAART therapy was initiated along with broad-spectrum antibiotics.

Investigations

CT of chest done on second hospital admission demonstrated bilateral airspace disease with areas of dense confluent consolidation and multiple satellite nodular opacities in a tree-in-bud distribution (figure 2). Sputum and blood cultures, alongside a respiratory viral panel, were all negative. A repeat bronchoscopy demonstrated diffusely hyperaemic mucosa and multiple maculopapular lesions (figure 3). A biopsy was not done due to the increased risk of bleeding, and bronchoalveolar lavage yielded negative results. This raised the suspicion for another opportunistic disease, with PJP unlikely due to negative cultures and lack of clinical response to antibiotic therapy.

Figure 2.

Chest CT demonstrating bilateral dense, confluent consolidations which resemble the typical ‘flame-shaped’ opacities.

Figure 3.

Bronchoscopy revealing diffuse macular hyperaemic lesions.

A thorough physical examination revealed a 2.0×1.0 cm violaceous nodule on his upper right thigh (figure 4). A punch biopsy confirmed KS. Correlating the clinical, imaging, bronchoscopy and pathology findings, pulmonary KS was diagnosed.

Figure 4.

2 cm×1 cm violaceous papule at the left lateral thigh found to be cutaneous Kaposi sarcoma.

Differential diagnosis

On presentation, the patient was initially thought to have bacterial versus viral pneumonia, given the bilateral infiltrates on chest imaging. Due to his cachectic appearance and the typical bilateral infiltrates on imaging studies, an HIV test was done, which resulted in positive. The differential diagnosis was broadened at that point, also to include fungal and mycobacterial infections.

As the patient failed to improve with antibiotic therapy, PJP was thought to be less likely on his second admission. A second bronchoscopy revealed global hyperaemia with multiple maculopapular lesions. At this point, KS was included in the differential, which prompted a comprehensive full-body exam. A single violaceous papule was discovered and biopsied, confirming KS.

Treatment

HAART with dolutegravir, tenofovir and emtricitabine was initiated as soon as pulmonary KS was diagnosed. The oncology team planned to start inpatient chemotherapy, targeting symptomatic pulmonary KS; however, the patient’s clinical status rapidly deteriorated, requiring intubation and admission to the intensive care unit 48 hours later. HAART was continued along with supportive treatment throughout his admission.

Outcome and follow-up

Two days after initiation of HAART, the patient’s respiratory status rapidly deteriorated, requiring intubation, ventilation and admission to the intensive care unit. However, the patient subsequently expired due to progressive respiratory failure 6 days after intubation, completing a total of 8 days of HAART.

Discussion

KS is a low-grade angioproliferative tumour that is caused by human herpesvirus 8 (HHV-8). With HIV progressing to AIDS, patients are at an increased risk of symptomatically manifesting HHV-8 infection in the form of KS. The AIDS-associated epidemiological form classifies it as an opportunistic disease occurring in the setting of severe immune dysregulation.² It is a multifocal neoplasm that can affect the skin, mucosa and viscera. KS occurs through the infection of endothelial cells by HHV-8, which leads to uncontrolled angiogenesis and inflammation.^{2 3} Clinically, this manifests as hyperpigmented vascular lesions with a variable degree of irritation of the affected organ. Cutaneous KS is the most common subtype, present in most cases of visceral involvement. With the advent of HAART, the overall incidence of KS has declined to <500 cases per 100 000 person years.⁴ Pulmonary KS primarily affects the airways and parenchyma, labelled as endobronchial KS, in addition to the pleural spaces and lymph nodes.⁵ The incidence of pulmonary KS is under-reported as it is easily misdiagnosed, with a prior studying revealing an incidence of 8% among total KS cases.⁴ Common symptoms include the subacute onset of dyspnoea, non-productive cough, pleuritic chest pain, along with fever and malaise. It can also progress to haemoptysis and progressive respiratory failure if left untreated.^{5 6} The incidence of pulmonary KS is well correlated with decreasing CD4 counts, mostly when the CD4 count is below 200 cells/mm³.⁷

Pulmonary KS should be considered in immunocompromised patients with persistent respiratory symptoms whose initial workup is inconclusive. This applies especially to patients with a subacute presentation of dyspnoea, dry cough and haemoptysis. The presence of characteristic skin lesions should raise the index of suspicion even further, as the coincidence is high. CT imaging usually demonstrates characteristic findings of bilateral, flame-shaped opacities with a bronchovascular distribution, which correlates with the endobronchial predilection for KS lesions. Other findings include perihilar infiltrates, hilar lymphadenopathy, pleural effusions and interlobular septal thickening.^{8 9} A bronchoscopy usually follows to rule out other infectious etiologies through bronchoalveolar lavage sampling. On direct inspection, bronchoscopy may reveal global hyperaemia and bloody mucosa, with scattered hyperpigmented maculopapular lesions in the upper and lower airways.¹⁰ This can explain the progressive hemoptysis present in many patients. A biopsy can be done for confirmation but is associated with a high risk of bleeding and is frequently avoided. Pulmonary KS can be diagnosed by correlating the characteristic imaging and bronchoscopy findings with the clinical presentation.^{3 4 6} If present, a biopsy of the cutaneous lesions can heavily support the diagnosis and is encouraged due to its lower risk. KS is mainly treated with rapid initiation of HAART, which has shown moderate success. Chemotherapy is usually added in the presence of significant symptoms in the context of visceral involvement and the absence of response to initial treatment.¹¹

Opportunistic infections in HIV/AIDs are well correlated with CD4 count. In many situations, compounding pathognomonic presentations with laboratory values can yield the diagnosis. In our case, the imaging and bronchoscopy findings led to a diagnosis of pulmonary KS, which was supported by a positive skin biopsy. This case highlights the importance of a broad differential in immunocompromised patients presenting with respiratory symptoms and the need for a thorough investigative workup. The clinical presentation of pulmonary KS is similar to PJP, and a high index of suspicion is required for diagnosis. In addition to this, the new era of the COVID-19 pandemic has brought one more differential to the table. Infection with SARS-CoV2 may manifest with similar lung findings on imaging, as PJP or pulmonary KS. This may further increase the difficulty of reaching the correct diagnosis, hence the importance of keeping a broad differential in these patients.

Learning points.

• Patients with HIV/AIDS are at increased risk of opportunistic respiratory infections. A broad differential diagnosis with a very thorough physical exam and a detailed workup is paramount for management.

• Pulmonary Kaposi sarcoma is rare and can easily be misdiagnosed as Pneumocystis jirovecii pneumonia on a plain chest X-ray. Its diagnosis requires a high index of suspicion.

• Pulmonary Kaposi sarcoma can be diagnosed by correlating clinical findings, imaging and gross bronchoscopy findings. A biopsy may help confirm the diagnosis.