Primary cutaneous nocardiosis in a patient with Evans’ Syndrome

ARTICLE

Auteur(s) : Tetsuya Moriue¹, Kozo Yoneda¹, Junko Moriue¹, Kozo Nakai¹, Ikumi Yokoi¹, Natsuko Fujita¹, Izumi Miyamoto¹, Katsuharu Kittaka², Hiroaki Dobashi², Yasuo Kubota¹

¹Department of Dermatology, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, 761-0793 Kagawa, Japan
²Department of Internal Medicine, Division of Endocrinology and Metabolism, Hematology, Rheumatology and Respiratory Medicine, Faculty of Medicine, Kagawa University, Kagawa, Japan

A 44-year-old Japanese man was diagnosed with Evans’ syndrome, a combination of autoimmune hemolytic anemia and immune thrombocytopenia [1], in 1988. In September 2007, he had severe bleeding due to exacerbation of Evans’ syndrome. Clinical examination revealed severe thrombocytopenia and normocytic anemia, and a markedly elevated level of platelets associated with IgG (PA-IgG). He was treated with high-dose corticosteroid pulse therapy, intravenous immunoglobulin, and rituximab at a dose of 375 mg/m² once a week for a total of two doses. His hematological condition was then controlled with oral prednisolone 17.5 mg/day.

He presented to our outpatient clinic with diffuse erythema on his left forearm in December 2007. Two weeks before this consultation, the patient fell down while hiking, and injured his left hand slightly. Then, diffuse erythema, swelling, and local heat appeared around the wound. The tentative diagnosis was cellulitis or lymphangitis. One week after treatment with intravenous administration of cephalosporine, he noticed three tender erythematosus nodules, where diffuse erythema with swelling was improved (figure 1A, arrowheads). From these nodules, on surgical incision, a milky white fluid discharge was observed. A skin biopsy from the nodule showed an abscess with infiltration of massive neutrophils and histiocytes except for giant cells in the dermis (figure 1B). However, hematoxylin-eosin, Gram, Grocott, or PAS staining in the biopsied-skin specimen detected no bacilli. Bacterial staining of the smear from the discharge showed Gram-positive filamentous-branched bacilli (figure 1C). Based on physiological characteristics, the culture of the discharge revealed Nocardia brasiliensis which could hydrolyze casein, tyrosine, and xanthine. No other fungus or acid-fast bacilli were detected in culture. We excluded systemic infection, because a chest radiograph and CT scan of the brain were normal, and he was healthy.

The patient was given oral trimethoprim (400 mg/day) -sulfamethoxazole (80 mg/day), and surgical incision of all nodules. After two weeks, treatment was changed to oral minocycline (100 mg/day) and intravenous amikacin (100 mg/day), because thrombocytopenia was observed as a side effect of trimethoprim-sulfamethoxazole. After three weeks, all nodules were flattened. Redness and local heat disappeared. Only minocycline was continued for two additional months, leading to a complete resolution of the nodules.

Nocardiosis is an opportunistic infection caused by genus Nocardia, a gram-positive, weakly acid-fast, branched-filamentous, aerobic actinobacteria [2]. Because Nocardia are ubiquitous in the environment, such as in soil, our case could be a case of lymphocutaneous infection inoculated by the injury.

Although primary cutaneous infections may be caused by any species of Nocardia, N. brasiliensis is isolated in 80% of cases of primary cutaneous nocardiosis as well as our case [2]. Other species such as N. asteroids and N. farcinica cause more severe infection, including pulmonary disease. In some cases, N. brasiliensis induces pulmonary or cerebral infections [3].

To date, six cases of nocardiosis associated with Evans’ syndrome have been reported, including our case (table 1). Five other cases besides our case revealed pulmonary or disseminated infections, and three patients died. These cases were caused by N. asteroids, N. farcinica, and unknown origin. All patients were treated with corticosteroid therapy, and three patients had other immunosuppressive agents added for Evans’ syndrome. Interestingly, 5 of 6 reports were from Japan. The reason may be coincidence, or due to a geographical distribution. It remains to be elucidated.
Table 1 Reported cases of nocardiosis with Evans’ syndrome. Note all cases, except our case, had pulmonary or other disseminated infections

Kundahara et al. reported cerebral nocardiosis in a patient with non Hodgkin’s lymphoma treated with rituximab [6]. The onset of their case was after one month of the rituximab treatment, while in our case, it was after two months of rituximab. We concluded that prolonged corticosteroid and intravenous rituximab therapy were the triggers of Nocardia infection in the present case.

Acknowledgements

References

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