The First Report of Bartonella quintana Immune Reconstitution Inflammatory Syndrome Complicated by Jarisch-Herxheimer Reaction

Abstract

Bacillary angiomatosis (BA) is a rare complication of human immune deficiency virus (HIV) infection in the post-antiretroviral therapy (ART) era, and few cases of BA-associated immune reconstitution inflammatory syndrome (IRIS) have been described. We report the case of a 50-year-old man who presented with mass lesions involving the skin, subcutaneous tissues, muscle, and bone. The diagnosis of Bartonella quintana BA was confirmed by serum polymerase chain reaction. The patient’s treatment course was complicated by both IRIS and Jarisch-Herxheimer reaction. The case had a favorable outcome with supportive care and continuation of ART and doxycycline.

Introduction

A rare opportunistic infection among immunosuppressed patients, bacillary angiomatosis (BA) presents with vasoproliferative mass lesions in multiple systems. It was recognized as a distinct but rare syndrome early in the AIDS epidemic; however, there are few case reports of BA immune reconstitution inflammatory syndrome (IRIS) in the post-antiretroviral therapy (ART) era. We report the first case of Bartonella quintana infection complicated by IRIS and Jarisch-Herxheimer reaction.

Case Report

A 50-year-old man originally from Ecuador presented for evaluation of a new diagnosis of human immune deficiency virus (HIV) and 4 months of progressive 15-kg weight loss and musculoskeletal pain. Six weeks prior to evaluation in the HIV clinic, he had been referred to hematology for new anemia and suspected malignancy. Workup at that time was notable for hemoglobin of 7.1 g/dL, CD4 count of 55 cells/mm³, and HIV viral load of 420 000 copies/mL. A bone marrow biopsy showed no evidence of malignancy. Positron emission tomography–computed tomography revealed several avidly enhancing lymph nodes and intramuscular masses in the right pectoralis and the left proximal vastus intermedius muscles. Core biopsy of the thigh mass showed increased vascular proliferation with reactive and plump endothelium in a background of neutrophilic and lymphoplasmacytic infiltrate (Figure 1).

Figure 1.

Biopsy of left thigh mass showing vascular proliferation with reactive and plump endothelium (black arrow) in a background of neutrophilic and lymphoplasmacytic infiltrate (white arrow).

Upon evaluation in HIV clinic, the patient had a temperature of 37.9°C. Tender masses palpated in the right pectoralis muscle, left anterior thigh, and left knee. In addition, 2 subcentimeter, dusky-appearing, cutaneous nodules were noted on the right posterior neck and left posterior thigh. He was initiated on atazanavir, ritonavir, emtricitabine/tenofovir, and trimethoprim–sulfamethoxazole (TMP-SMX) prophylaxis.

Seven days after starting ART, the patient presented with worsening neck pain and fever. He was febrile (at 39.3°C), tachycardic, and hypotensive. The tenderness and size of the subcutaneous and cutaneous masses had progressed, most notably of the knee mass and thigh skin nodule (Figure 2A and B). Imaging of the cervical and thoracic spine revealed cortical erosion of the left posterior aspect of C4 with an extra-axial soft tissue density.

Figure 2.

A, Left lateral knee mass. B, Left thigh subcutaneous nodule.

The patient was started on broad-spectrum antimicrobials and admitted to the hospital. Given a high suspicion for BA, he was also initiated on doxycycline. The next day, the patient developed a diffuse morbilliform rash, and broad-spectrum antimicrobials and TMP-SMX were discontinued. Two days later, he developed hypotension and was transferred to the intensive care unit. His leukocyte count peaked at 36 600/µL from 9100/µL on admission. He remained febrile. Supportive care was provided for the Jarisch-Herxheimer reaction.

His condition improved on ART and doxycycline. A diagnosis of BA was confirmed by positive serum polymerase chain reaction for B quintana. Bartonella quintana serology sent to the Centers for Disease Control returned at 1:65 536. In follow-up after 3 months, the cutaneous, muscular, and bone lesions resolved. After 1 year of therapy, his absolute CD4 count increased to 213 cells/mm³, the and serial B quintana titers remained exceptionally high.

Discussion

The etiologic agents of BA, B quintana and B henselae, are fastidious, gram-negative, facultative intracellular bacilli with a tropism for erythrocytes and endothelial tissue. The characteristic vasoproliferative mass lesions of BA result from the production of proteins (BepA and BepA2) that induce an antiapoptotic state in endothelial collagen tissue, facilitating vascular proliferation. ^1,2 This process is facilitated by a dysfunctional immune response in immunosuppressed hosts, leading to dissemination of disease. ³

In a landmark case series of 49 patients with BA, Koehler et al described the differential predilection for organ system involvement between B quintana and B henselae. ⁴ As in our case, subcutaneous tissue and bone lesions were defining features of infection with B quintana. The involvement of muscle, either as a part of multisystem disease or as pyomyositis alone, has also been described in isolated cases. ^5,6

One of the most striking aspects of this case is the rapid progression of the patient’s condition within 1 week of starting ART. Bacillary angiomatosis IRIS has rarely been described in the post-ART era. ^{7 -10} Similar to our patient, the reported cases demonstrated symptoms and signs of BA prior to ART initiation; and in 1 case the IRIS event was fatal in the setting of airway compression from a neck mass. ⁷ A high microbial burden predisposed this patient to a marked Jarisch-Herxheimer reaction shortly after doxycycline initiation. This phenomenon has been described ¹¹ ; however, this is the first case reported in the setting of IRIS.

Conclusion

Bartonella quintana BA is an unusual multisystem disease that can be differentiated from B henselae on clinical grounds and is uncommonly encountered in the post-ART era. Although a rare event, BA IRIS can have severe manifestations, especially if mass lesions risk compressing critical anatomic structures. The additional complication of Jarisch-Herxheimer reaction in this unique case emphasizes the importance of intensive supportive care and antipyretic pretreatment for the management of disseminated BA in the immune reconstitution phase.