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Cutaneous Manifestations of Bartonellosis An Bras Dermatol. 2019;94(5):594---602 Anais Brasileiros de Dermatologia www.anaisdedermatologia.org.br REVIEW ଝ,ଝଝ Cutaneous manifestations of bartonellosis a,b a,b Karina de Almeida Lins , Marina Rovani Drummond , b,c,∗ Paulo Eduardo Neves Ferreira Velho a Department of Clinical Medicine, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil b Laboratory of Applied Research in Dermatology and Bartonella Infection, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil c Discipline of Dermatology, Department of Clinical Medicine, School of Medical Sciences, Universidade Estadual de Campinas, Campinas, SP, Brazil Received 4 June 2018; accepted 27 February 2019 Available online 2 October 2019 Abstract Bartonellosis are diseases caused by any kind of Bartonella species. The infec- KEYWORDS tion manifests as asymptomatic bacteremia to potentially fatal disorders. Many species are Bartonella; pathogenic to humans, but three are responsible for most clinical symptoms: Bartonella Skin diseases; bacilliformis, Bartonella quintana, and Bartonella henselae. Peruvian wart, caused by B. bacil- Neglected diseases liformis, may be indistinguishable from bacillary angiomatosis caused by the other two species. Other cutaneous manifestations include maculo-papular rash in trench fever, papules or nod- ules in cat scratch disease, and vasculitis (often associated with endocarditis). In addition, febrile morbilliform rash, purpura, urticaria, erythema nodosum, erythema multiforme, ery- thema marginatus, granuloma annularis, leukocytoclastic vasculitis, granulomatous reactions, and angioproliferative reactions may occur. Considering the broad spectrum of infection and the potential complications associated with Bartonella spp., the infection should be considered by physicians more frequently among the differential diagnoses of idiopathic conditions. Health professionals and researchers often neglected this diseases. © 2019 Published by Elsevier Espana,˜ S.L.U. on behalf of Sociedade Brasileira de Dermatologia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/ by/4.0/). ଝ How to cite this article: Lins KA, Drummond MR, Velho PE. Cutaneous manifestations of bartonellosis. An Bras Dermatol. 2019;94:594---602. ଝଝ Study conducted at the Laboratory of Applied Research in Dermatology and Bartonella Infection, School of Medical Sciences, Universi- dade Estadual de Campinas, Campinas, SP, Brazil. ∗ Corresponding author. E-mail: [email protected] (P.E. Velho). https://doi.org/10.1016/j.abd.2019.09.024 0365-0596/© 2019 Published by Elsevier Espana,˜ S.L.U. on behalf of Sociedade Brasileira de Dermatologia. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). Cutaneous manifestations of bartonellosis 595 Introduction infection. These data warn of the risk of expansion of Car- rion’s disease due to the possible adaptation of vectors in 1 areas inhabited by these animals, which may serve as dis- Bartonellosis are diseases caused by any Bartonella species. ease dispersal facilitators in neighboring endemic regions, They are neglected, re-emergent, and distributed world- 24 including Brazil. wide, affecting mainly populations suffering from poverty, The disease is biphasic, with an acute phase (Oroya with precarious sanitation, and that are in direct contact 2,3 fever) characterized by fever, hemolytic anemia, and tran- with arthropods and domestic animals. Most species cause 1,3 sient immunodeficiency and a chronic phase (Peruvian wart) zoonotic diseases. 1,25 marked by cutaneous vasoproliferative lesions. Bartonella spp. are fastidious Gram-negative bacilli, well The acute phase of the disease lasts from one to four adapted to a variety of animal reservoirs, particularly mam- weeks and severity can range from mild to fatal. Absence mals. These bacteria are capable of infecting and surviving of antibiotic treatment can lead to a mortality rate of up inside erythrocytes. The intraerythrocytic phase allows for a to 88%. This is caused by the massive invasion of erythro- protection niche for the agent, resulting in a prolonged and 4 cytes and initially leads to non-specific symptoms such as recurrent infection. The bacteria can also infect endothe- 5 malaise, drowsiness, headache, chills, fever, anorexia and lial cells. myalgia, which make the patient increasingly more jaun- The main route of transmission of Bartonella spp. is diced and confused. As the disease progresses, a severe from infected humans or animals to new hosts through hemolytic condition, accompanied by lymphadenopathy and blood-sucking arthropod vectors. Transmission through ani- hepatosplenomegaly, is established. Disease worsening can mal scratches has been reported but it is not certain, since 1,6 lead to acute respiratory distress, pericardial effusion, fleas are needed for transmission among cats. Recent myocarditis, endocarditis, delirium, seizures, coma and studies reinforce the hypothesis that these bacteria can be 1,9,25 multiple organ failure. transmitted through blood transfusion, which is a concern After an average of two months in the acute febrile for people all over the world since currently there is no 3,7---9 phase (which may not occur, particularly in natives of the preventive action against this possibility. In addition, endemic region) the Peruvian wart appears, an eruptive asymptomatic infection by Bartonella sp. has already been 3,8---18 cutaneous manifestation formed by angiomatous lesions, detected in blood donors. which is often clinically and histologically similar to lesions Bartonella spp. are responsible for a broad clinical spec- of bacillary angiomatosis (BA). These lesions may present trum, from asymptomatic bacteremia to potentially fatal as angiomatous lesions, papules, papule-tumors, or nod- presentations. Although the manifestations associated with ules. They appear in patches, predominantly on the face bartonellosis have increased considerably over the past and extremities, and measure 0.2---4 cm in diameter. They decades, physicians usually do not consider the possibility of may persist for months or even years, and can be accom- infection with these bacteria among differential diagnoses, panied by fever, bone, and/or joint pains. The severity of except in cases with localized lymph node enlargement or 19,20 the eruption is variable and it appears not to be related to endocarditis with negative culture, which suggests that previous antibiotic treatment. This is the tissue phase of Car- bartonellosis has been neglected by the medical community, 26 rion’s disease and is self-limiting. Although not fatal, if left leaving many cases undiagnosed. untreated, these lesions persist as pathogen reservoirs and a source of contagion through the vector. This infection is usu- Clinical aspects ally treated with rifampicin, although streptomycin is also effective and was the drug of choice before 1975. Peruvian Among the 16 species of Bartonella that are pathogenic to wart does not respond to treatment with chloramphenicol or humans, three are responsible for the majority of clinical penicillin. Treatment alternatives include ciprofloxacin and 27 symptoms: Bartonella bacilliformis, Bartonella quintana, azithromycin associated with deflazacort. It does not lead 5,21 28,29 and Bartonella henselae. to scarring, except when there is secondary infection. Until 1993, B. bacilliformis was considered the only Histologically, Peruvian wart lesions show a proliferation species of this genus. It is the etiologic agent of Car- of endothelial cells of the terminal vasculature in the dermis rion’s disease, previously known as the only bartonellosis. and subcutis. The acute and chronic inflammatory infiltrate B. bacilliformis is transmitted by the female Lutzomyia ver- that accompanies the presence of B. bacilliformis in the rucarum, endemic in the Peruvian Andes and regions of interstice and inside the endothelial cells is an important Ecuador and Colombia. finding, even in non-ulcerated lesions. The lesions can have Reports in recent decades of outbreaks in regions of more differentiated and ectatic vessels that are clinically atypical altitude strongly suggest epidemiological areas as and histologically similar to pyogenic granuloma. Cellular potential for expansion. Current climate changes associated atypia can be seen, particularly in more solid lesions, with with human activities have contributed to the resurgence of imperceptible lumens and spindle cells that resemble Kaposi 30 infection and its expansion into new areas. Climate changes sarcoma. affect vector distribution and, additionally, phenomena such B. quintana was initially associated with trench fever as El Nino˜ have caused an increase in humidity levels, which (TF), characterized by recurrent febrile episodes. Currently favors the reproduction of vectors and the occurrence of reported in hikers, alcoholics, and AIDS patients in the 22,23 outbreaks. Some studies envolving animals to search for United States and Europe, the disease has been consid- potential new hosts have shown that some species of apes ered as re-emergent and is the agent implicated in cases in the jungles of South America, such as the Feline Night of chronic bacteremia, endocarditis, and BA. Humans are Monkey (Aotus infulatus), are susceptible to B. bacilliformis the only known reservoirs and the transmission among them 596 Lins KA et al. Immunocompetent patients infected with B. henselae can develop cat
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