Cutaneous manifestations in brucellosis.

Brucellosis is a common worldwide zoonotic disease. Cutaneous manifestations are not specific and affect 1-14% of patients with brucellosis. Here, we describe 49-year-old female with fever and a diffuse maculopapular rash due to Brucella melitensis infection. Histopathology of skin biopsy revealed leukocytoclastic vasculitis; positive blood cultures for B. melitensis established the diagnosis of brucellosis. We provide a review of the relevant literature.

Introduction

Brucellosis is an infection caused by bacteria of the genus Brucella. There are four species of Brucella that cause infection in humans. The most pathogenic is Brucella melitensis. Human infection results from occupational contact with an infected animal or by ingestion of infected milk products or tissues. Person-to-person transmission rarely, if ever, occurs. After invading the body, Brucella is phagocytized by polymorph nuclear leukocytes and macrophages. Organisms spread via lymphatics to regional lymph nodes and, if not contained, to the bloodstream. Bacteremia may result in foci in cells of the reticuloendothelial system in the liver, spleen, and bone marrow, and the other organs such as the kidneys.[1]

Brucellosis may be asymptomatic with only serologic evidence of infection. The manifestation of symptomatic brucellosis may be divided into acute brucellosis, localized disease, and chronic brucellosis. Localized disease may occur at almost any anatomic location, but osteomyelitis, splenic abscess, genitourinary tract infection, pulmonary disease, and endocarditis are among the more common.[1] Cutaneous manifestations are nonspecific and their prevalence is reported to range between 1 and 14% of patients with brucellosis.[23]

Here, we describe 49-year-old female with cutaneous manifestation (leukocytoclastic vasculitis) as an unusual presentation of brucellosis.

Case Report

A 49-year-old woman was admitted to hospital after a 3-week period of an intermittent fever, fatigue, and nausea and vomiting. The physical examination revealed high fever and splenomegaly which was confirmed by an abnormal ultrasound scan. Laboratory tests showed the following values: hematocrit 28%; WBC 2650 cells/mm3, platelet count 52,000 mm3. Serological and blood cultures were obtained on admission. Bone marrow biopsy was planned but as disseminated urticarial and maculopapular lesions developed [Figure 1], bone marrow biopsy was delayed and biopsy from skin lesions was done. Histopathology of a skin biopsy revealed supporting results with infectious process. Excisional skin biopsy results were assessed as leukocytoclastic vasculitis. Serological tests for salmonellosis, Epstein-Barr virus (EBV), HIV and hepatitis B were negative. Brucella agglutinin titer was positive at 1/200 titration (4+). Blood cultures are positive, that means Brucella reproduced. After a diagnosis of brucellosis was made, the patient was administered doxycycline 100 mg per os twice daily for 6 weeks, and rifampicin 600 mg per os once daily, beginning on the 10th day of hospitalization. Six days after treatment, the fever came down and the skin lesions vanished.

Figure 1

Maculopapular lesions on the abdomen and knee

Discussion

Brucellosis is a systemic infection in which any organ or system of the body can be involved. Cutaneous lesions occur in about 5–10% of patients with brucellosis.[4] The cutaneous manifestations of brucellosis can be multiple and are due to direct inoculation, hypersensitivity phenomena, deposition of immune complexes and direct invasion by the organism reaching the skin hematogenously.[2-5]

Ariza et al., in a review of 436 cases of brucellosis, reported that about 6% of the patients had cutaneous lesions probably caused by the disease and described disseminated violet erythematous, papulonodular eruption, and erythema nodosum-like lesions as the most frequent eruptions observed, which appear during the initial episode of the disease or in relapse.[2] Chronic ulcerations and subcutaneous abscesses have also been described in brucellosis.[6] Al Abdely et al. described a case of female patient with a breast abscess caused by B. melitensis, which was successfully treated with co-trimoxazole plus doxycycline for 3 months.[7]

The patient in our case had fever, splenomegaly and pancytopenia. Her blood and urine cultures were negative; however, Brucella agglutinin titer was positive at 1/200. Maculopapuler rash developed after 2 days of her admission. Skin lesions were nonpruritic, and there was no clinical or laboratory evidence of a hypersensitivity reaction (e.g. eosinophilia). Histological examination of skin biopsy with immune-fluorescence revealed infectious process and assessed the condition as a leukocytoclastic vasculitis.

Vicaro et al. reported a 29-year-old woman suffering from brucellosis, who developed maculonodular and purpuritic lesions. The skin biopsy showed granulomatous vasculitis with no deposition of immunoglobulins and complement of vessels. Maculonodular eruption was associated with purpura, secondary to Brucella abortus infection.[8] Like our case, Nagore et al. described a 22-year-old man presenting with brucellosis, with leukocytoclastic vasculitis as a cutaneous manifestation. Skin lesions resolved 48 hours after starting treatment tetracycline and rifampicin.[9] Our patient was treated with doxycycline 100 mg per os twice daily for 6 weeks, plus rifampicin 600 mg. Two days after the treatment had been initiated, the skin lesions vanished.

Brucellosis remains an important public health problem in Turkey. In a study by Akcalι et al ., they determined the types and rates of cutaneous lesions that occur in patients with brucellosis. A total of 140 patients who had been diagnosed with brucellosis were prospectively observed in the dermatology clinic. Cutaneous findings related to brucellosis were observed in 8 (5.71%) of the 140 cases. Maculopapular eruptions were observed in 2 patients (25%), erythema nodosum-like lesions in 2 (25%), psoriasiform lesions in 1 (12.5%), palmar erythema in 1 (12.5%), malar eruption in 1 (12.5%), and palmar eczema in 1 (12.5%) patient. The investigators concluded that although cutaneous findings encountered in brucellosis are generally not specific to this disease, the presence of these findings may be useful in diagnosing brucellosis in persons who live in, or used to live in, endemic regions.[10]

In conclusion we emphasize that cutaneous lesions are not specific to brucellosis and may be seen in a variety of other dermatologic diseases caused by many agents; therefore, these agents should be kept in mind in the differential diagnosis in a country where the disease is endemic.