A 35-year-old man comes to the office due to concern that his HIV medication is no longer working. Over the last 6 weeks, the patient has had intermittent fevers and awakened several times drenched in sweat. He has not used injection drugs since he was diagnosed with HIV a year ago, and he lives in a house with other individuals recovering from substance use disorder. The patient takes antiretroviral therapy and trimethoprim-sulfamethoxazole. Temperature is 37.9 C (100.2 F), blood pressure is 126/72 mm Hg, and pulse is 102/min. Physical examination reveals several enlarged cervical, supraclavicular, and epitrochlear lymph nodes that are rubbery and mobile. Cardiopulmonary examination is normal, and no organomegaly is present on abdominal examination. There is no rash. Chest x-ray reveals an enlarged cardiac silhouette. Current CD4 count is 208/mm³ and the viral load is undetectable. Which of the following underlying pathogens is most likely responsible for this patient's symptoms?

Question

Quizplus · Accepted Answer

This patient with HIV has diffuse lymphadenopathy (LAD), intermittent fevers, and night sweats. Although this constellation of findings can be seen in untreated HIV, the presence of an undetectable viral load indicates compliance with antiretroviral therapy. Therefore, the differential diagnosis primarily includes hematologic malignancy, rheumatic disease, and other systemic infections. Given the presence of supraclavicular, epitrochlear, and mediastinal LAD, a lymphoid neoplasm such as non-Hodgkin lymphoma (NHL) is most likely. Patients with HIV are at a dramatically elevated risk of malignancy due to immune dysregulation and impaired cytokine signaling. This limits the ability of patrolling cytotoxic T-cells to induce apoptosis in cells that have accumulated genomic mutations. It also promotes reactivation of latent oncogenic viruses, which can cause AIDS-defining malignancies such as invasive cervical carcinoma (human papillomavirus), Kaposi sarcoma (human herpesvirus 8), CNS system lymphoma (Epstein-Barr virus [EBV]), and NHL. Approximately 10% of patients with AIDS develop NHL; nearly all cases in this population are linked to the reactivation of EBV and the subsequent production of oncogenic viral proteins. Major manifestations include diffuse LAD, which may involve the epitrochlear, supraclavicular, and mediastinal (enlarged cardiac silhouette) lymph nodes. B symptoms (eg, night sweats, fevers, weight loss) are generally present. Diagnosis is usually made by excisional lymph node biopsy. EBV is also associated with development of Hodgkin lymphoma, which can develop in patients with HIV, although NHL is more common in this population (possibly reflecting the immune interaction between Reed-Sternberg cells and nonmalignant inflammatory cells needed for the development of Hodgkin lymphoma). (Choice A) Bartonella henselae, the causative pathogen of catscratch disease, can cause regional LAD in the epitrochlear, supraclavicular, and cervical chains. However, the LAD is usually tender and erythematous, and mediastinal LAD is atypical. (Choice B) Cytomegalovirus is a common pathogen in patients with advanced AIDS; it frequently attacks the gastrointestinal tract and retina. Although this virus can cause an infectious mononucleosis-like illness with significant peripheral LAD (eg, cervical, axillary, inguinal), the presence of supraclavicular, mediastinal, and epitrochlear LAD is more consistent with a lymphoid malignancy (CMV is not oncogenic). (Choice D) Although hepatitis C virus causes chronic immune stimulation, which increases the risk for lymphoma, patients with AIDS develop NHL almost exclusively due to EBV reactivation. (Choice E) Human papillomavirus is oncogenic and contributes to invasive cervical and esophageal cancers. It has tropism for epithelial cells, not B-lymphocytes, so it does not increase risk of lymphoma. (Choice F) Toxoplasma gondii is a common cause of encephalitis in patients with advanced AIDS. Although disseminated toxoplasmosis can be associated with diffuse LAD, this patient is on prophylaxis (trimethoprim-sulfamethoxazole) for this infection. Educational objective: Patients with HIV are at significantly increased risk of malignancy due to immune dysregulation and reactivation of oncogenic viruses. One of the most common malignancies is non-Hodgkin lymphoma, which is due to the reactivation of the Epstein-Barr virus in B-lymphocytes. Patients generally present with diffuse lymphadenopathy and B symptoms.

A 35-Year-Old Man Comes to the Office Due to Concern