Gorgas Case 2023-09

History: A 77-year-old female patient presented with a one-month history starting with the appearance of papular lesions in the lower extremities, associated with malaise and loss of appetite. Two weeks before admission, she had intermittent fevers, quantified at 39°C. In the week before admission, she noted that the lesions started ulcerating with no discharge, and she noticed new lesions in her arms, so she decided to seek medical attention. No history of fever or night sweats.

Epidemiology: Born and lives in Churin, in the highlands of Lima (2250 m above sea level), in a house made of adobe, where she works as a homemaker. No use of bed nets or insect repellent.

Past medical history: Previously diagnosed with type 2 diabetes, receiving metformin 500mg bid.

Physical Examination: Normal vital signs. Multiple verrucous lesions with central ulceration and peripheral desquamation and a dark scab in the lower and upper limbs (Images A, B, C). Rest of exam was within normal limits.

Laboratory: Hb 12 g/dL, Hct 36%, Leu 6.66 (0% bands, 49.3% neutrophils, 2.5% eosinophils, 0.6% basophils, 10.4% monocytes, 35.7% lymphocytes). Urea 23 mg/dL, Creatinine 0.58 mg/dL, Na 130, K 4.6, Cl 93, CRP 48 mg/L.

UPCH Case Editors: Carlos Seas, Course  Director / Paloma Carcamo, Associate Coordinator
UAB Case Editors: David O. Freedman, Course Director Emeritus / German Henostroza, Course Director

Diagnosis: Carrion’s disease – eruptive phase (verruga peruana)

Discussion: Warthin-Starry silver stain of a skin biopsy taken at one of the lower limb lesions showed a reactive epidermis with nodular aggregates of histiocytes and endothelial cells, and scanty dark, curved bacilli (Image D) and a diagnosis of the eruptive phase of Carrion’s disease, known also as “verruga peruana” was made.

Carrion’s disease is a vector-borne disease that is endemic in some areas of the highlands in Peru, Colombia, and Ecuador at altitudes between 500-3200 meters where Lutzomyia spp sandflies are present, though El Niño and climate change may favorably affect vectors and change the geographic distribution of the disease¹. Carrion’s disease is caused by some species of Bartonella, including B. bacilliformis and the more recently described B. ancashi². It is typically described as a biphasic illness starting with a febrile phase known as Oroya fever and then followed by a chronic secondary eruptive phase, known as verruga peruana, in which nodular skin lesions appear. However, as is illustrated in the presented case, not all cases of verruga peruana are preceded by a febrile illness. One study conducted in the highlands in Ancash in Peru found that about 11% of cases of Bartonellosis presented with Oroya fever (particularly in individuals without immunity), 37% with verruga peruana and a history of recent fever, 32% with verruga without recent fever, and 21% with asymptomatic infection³. The presentation of verruga without a history of Oroya fever may be due to immunity from previous infections, but there is currently no evidence demonstrating this.

Verruga peruana typically occurs when bacilli invade capillary endothelial cells, producing lesions in the skin and mucous membranes that can be miliary, mular or nodular. They are typically non-tender and purplish in color and can persist for a long time, and may be accompanied by systemic symptoms such as malaise, arthralgias or fever. These lesions can be similar in appearance to those seen in Kaposi’s sarcoma and bacillary angiomatosis as all are caused by capillary proliferation and endothelial cell hyperplasia. However, both of these would be seen in immunosuppressed patients and the histopathological findings would be different. Other skin conditions that may mimic verruga peruana include yaws, pyogenic granuloma, and cutaneous tuberculosis or atypical mycobacterial infections.

The diagnosis of Bartonellosis is challenging, one study conducted at our institution showed that 19% of patients with verruga peruana and 12% of patients with Oroya fever were initially misdiagnosed4. Scanty studies have been undertaken assessing the yield of techniques such as indirect fluorescence antibody tests (IFAs), PCRs, ELISAs, sonicated immunoblots and Western Blots, with varying results. The most widely employed technique is still the thin blood smear, which has been reported to be positive in as little as 13% of verruga peruana cases⁴. Blood cultures are usually positive in Oroya fever but take an average of 18 days to be positive so their clinical utility may be limited. Nonetheless, they are important to document infection and rule out concomitant bacterial secondary infections, which are common. Post-eruptive patients may have persistently positive blood cultures for Bartonella, as may asymptomatic seropositive people, which has important implications for control⁵.

Treatment for the chronic phase of Carrion’s disease usually consists of a 7-day course of azithromycin, though a 14-to-21-day course of rifampin or 7-to-10-day course of ciprofloxacin may also be acceptable. It is important to treat patients with the chronic form of Carrion’s disease as they may act as a reservoir for the bacteria and play an important role in transmission of the disease..

References:
1. Clemente NS, Ugarte-Gil CA, Solórzano N, et al. Bartonella bacilliformis: A Systematic Review of the Literature to Guide the Research Agenda for Elimination. PLOS Neglected Tropical Diseases. 2012;6(10):e1819. doi:10.1371/journal.pntd.0001819
2. Blazes DL, Mullins K, Smoak BL, et al. Novel Bartonella Agent as Cause of Verruga Peruana. Emerg Infect Dis. 2013;19(7):1111-1114. doi:10.3201/eid1907.121718
3. Chamberlin J, Laughlin LW, Romero S, et al. Epidemiology of endemic Bartonella bacilliformis: a prospective cohort study in a Peruvian mountain valley community. J Infect Dis. 2002;186(7):983-990. doi:10.1086/344054
4. Maguina C, Garcia PJ, Gotuzzo E, Cordero L, Spach DH. Bartonellosis (Carrión’s disease) in the modern era. Clin Infect Dis. 2001;33(6):772-779. doi:10.1086/322614
5. Minnick MF, Anderson BE, Lima A, Battisti JM, Lawyer PG, Birtles RJ. Oroya Fever and Verruga Peruana: Bartonelloses Unique to South America. PLoS Negl Trop Dis. 2014;8(7):e2919. doi:10.1371/journal.pntd.0002919