Cutaneous bacillary angiomatosis in the setting of immunosuppression: A rare case in a heart transplant recipient

Abstract

Bacillary angiomatosis is a rare, opportunistic infection caused by Bartonella spp. In the skin, neovascular proliferation results in erythematous and violaceous papules and nodules. While there are many reports of bacillary angiomatosis in solid organ transplant recipients, only two cases are documented in cardiac transplant recipients. Herein, we report a case of bacillary angiomatosis in a 67-year-old male post-orthotopic cardiac transplant who presented with erythematous papules scattered on the chest, back, and extremities. Biopsies revealed lobular capillary proliferation in the superficial dermis and positive Warthin–Starry staining. Nucleic acid amplification by PCR identified Bartonella quintana. After completing a 3-month course of doxycycline 100 mg twice daily, the patient had complete resolution of skin findings. The rise in solid organ transplants, combined with the expanding repertoire of immunosuppressive therapies, has significantly improved patient survival. However, it has also created a favorable environment for opportunistic infections, including bacillary angiomatosis, to emerge as a growing concern.

Introduction

Bacillary angiomatosis (BA) is a rare opportunistic infection caused by Bartonella henselae or Bartonella quintana infection. ¹ In the skin, neovascular proliferation results in erythematous and violaceous papules and nodules that can become crusted or ulcerated. ¹ Cats are believed to be the main reservoir for B. henselae, spreading what is known as “cat-scratch disease,” whereas B. quintana is transmitted among humans by louse as was the case during the spread of “trench fever” during World War I. ²

Bartonella infection occurs primarily in immunocompromised hosts. BA was first reported in patients infected with human immunodeficiency virus (HIV) with low CD4 counts.^1,3 Since then, BA has been reported in solid organ transplant recipients (SOTR), now more frequently than in HIV patients due to the development of antiretroviral therapies. ³ In recent years, solid organ transplant procedures have increased exponentially with recipients living longer than ever before. ⁴ However, to prevent host rejection of transplanted organs, indefinite administration of immunosuppressive agents is required resulting in high patient susceptibility to various infections. ⁴

While BA pathophysiology is known, further research is needed to explore its occurrence in relation to solid organ transplant, and more specifically in relation to heart transplant. While there are many reports of BA in SOTR, only two cases are documented in heart transplant recipients. Herein, we present the following case of a cutaneous BA in a heart transplant recipient.

Case report

A 67-year-old heart transplant recipient on mycophenolate mofetil and tacrolimus presented to clinic with a painless, nonpruritic, papular rash. Clinical examination revealed multiple erythematous dome shaped papules on the chest, back, and extremities. Skin biopsy revealed lobular capillary proliferation in the superficial dermis with ectatic vessels lined by reactive endothelium and scattered leukocytoclastic debris. The infiltrate included admixed plasma cells, lymphocytes, neutrophils, and histiocytes. Warthin–Starry stain identified rod-shaped bacteria consistent with Bartonella. Further workup including serology and PCR confirmed B. quintana to be the cause of infection. Endocarditis and intra-abdominal infection were ruled out via echocardiogram and ultrasound of the abdomen. The patient lacked any systemic symptoms to suggest visceral involvement and blood cultures were negative, thereby confirming infection was restricted to the skin. After completing a 3-month course of doxycycline 100 mg twice daily, the patient had complete resolution of skin findings.

Discussion

Cases of BA following solid organ transplant have been reported in renal transplant recipients however, reports of BA in heart transplant recipients are rare.^3,5–8 In 2012, a 65-year-old man who received a heart transplant 2 years prior tested positive for B. henselae while presenting with a fever and a single erythematous nodule. ⁹ While PCR for Bartonella of the skin lesion was negative, it was noted that testing was conducted 2 weeks following initiation of antibiotics which might have affected results. ⁹ While the nodule was ultimately diagnosed as squamous cell carcinoma, this was reported to be the first case of Bartonella in a heart transplant recipient. ⁹ In 2016, a 68-year-old female heart transplant patient presented with acute onset of BA from B. quintana along the trunk and arms which resolved completely following a 4-month course of doxycycline. ¹⁰ Similarly, a 50-year-old man who underwent a heart transplant 10 years prior presented with disseminated BA from B. quintana approximately 1 year after also receiving a renal transplant which resolved following treatment with doxycycline. ¹ To our knowledge, these are the only other cases of BA in a heart transplant patient in peer-reviewed literature.

Interestingly, the most common source of infection associated with BA is B. henselae related to cat scratches or bites. ¹⁰ While B. henselae is a common cause of BA, all reported cases in heart transplant recipients have been caused by B. quintana.^1,10 This form of BA is often associated with body lice when people lack access to adequate hygiene. ² While the patient did not have any exposure to this, the donor was at risk. However, the donor tested negative for Bartonella by serology. Nevertheless, the donor was thought to likely be the source of infection given the known limitations of serology.

B. quintana infection has rarely been transmitted via solid organ transplantation; however, in 2023, a cluster of 6 recipients from 11 seropositive Albertan unhoused deceased donors developed bartonellosis secondary to B. quintana. ¹¹ Of the six recipients, four developed BA. ¹¹ None of these patients were heart transplant recipients. ¹¹ Health Canada alerted Canadian organ transplantation programs of this outbreak noting that it coincided with concurrent epidemics of drug overdose and homelessness. ¹² As receipt from an organ donor who experienced homelessness within the last 12 months was the most common factor among those infected with B. quintana, it was recommended that previous homelessness be included in organ donor surveys and its impact be assessed in future studies. ¹²

If untreated, BA can affect the liver, spleen, gastrointestinal tract, and heart, resulting in significant morbidity and mortality. ¹⁰ Heart transplant recipients are particularly vulnerable to BA as cardiac involvement could compromise function and/or trigger rejection of the donor heart. The rise in solid organ transplants, combined with the expanding repertoire of immunosuppressive therapies, has significantly improved patient survival. However, it has also created a favorable environment for opportunistic infections, including BA, to emerge as a growing concern.

Our experience contributes to the growing evidence that BA is a concern among SOTR and highlights that B. quintana is the predominant source of infection among heart transplant recipients. Additional research relating to donor transmitted Bartonella infection is needed to better understand BA in the context of heart transplant recipients.