¹The University of Texas MD, Anderson Cancer Center, Houston, TX, USA

Toxoplasma gondii can lead to serious life-threatening infections in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT).^{1, 2} The overall prevalence of toxoplasmosis in stem cell transplant recipients range from <0.5% in the United States up to 3–5% in Europe where infection rates are higher in the general population.^{3, 4, 5} T. gondii reactivation mainly involves the central nervous system. Pneumonia may occur occasionally, however, skin involvement is rare even in severely immunosuppressed individuals.^{6, 7} We present a patient who developed multiple skin lesions during the early post transplant period.

A 37-year-old man from Mexico presented with fever, cough, and intermittent headache 5 days after undergoing HLA-matched unrelated donor marrow transplantation for refractory acute lymphocytic leukemia. He had diabetes mellitus and had worked as a welder on construction sites in Houston, Texas for 2 years. Despite broad-spectrum antimicrobial and antifungal therapy, the patient's fever continued to rise (40°C). His fever was accompanied by severe hypoxemia and interstitial infiltrates on chest radiograph that were consistent with diffuse alveolar hemorrhage. A new skin rash was noted on the 8th transplant day. On examination, patients was ill appearing and had greater than 50 nonvesicular, pleomorphic papular skin lesions on extremities, torso, abdominal wall, and face; these lesions were discrete, circumscribed with no accompanying induration or central necrosis (Figure 1). The laboratory values were as follows: white cell count 200 cells/l, platelet count 38 000 cells/l, serum creatinine 0.5 mg/dl, lactic dehydrogenase 4279 IU/l, alkaline phosphatase 525 IU/l, and alanine aminotransferase 634 IU/l.

Figure 1.

Pleomorphic, nonvesicular lesions are noted on patients right forearm (top panel), forehead and scalp (bottom panel).

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All cultures including blood, cerebrospinal fluid, and bronchoalveolar lavage remained sterile. A skin biopsy of right forearm lesion showed multiple T. gondii bradyzoites in the epidermis (within keratinocytes, Figure 1, arrowhead, panels a and b, 200 and 400, respectively) and with dermal blood vessels (Figure 2, arrowhead, panel c, 400). Toxoplasma was confirmed by immunohistochemical study. Skin biopsy of lesions over the abdominal wall showed leukocytoclastic vasculitis; T. gondii was not seen. Owing to a sulfa allergy, treatment with clindamycin (900 mg three times daily) and pyrimethamine (100 then 50 mg daily) was initiated. Giemsa stain of bronchioalveolar lavage was negative, and the patient had nonreactive T. gondii serology (IgG, IgM). Magnetic resonance imaging of the brain revealed no central nervous system lesions, and the results of a lumbar puncture were within normal limits.

Figure 2.

Hematoxylin- and eosin-stained sections of right forearm skin biopsy showed T. gondii bradyzoites in the epidermis within keratinocytes, panels a and b, 200 and 400 magnification, respectively. In panel c, T. gondii tachyzoites are noted within the dermal blood vessels ( 400 magnification).

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On day 13, his fever had resolved, although progressive respiratory failure requiring assisted ventilation, presence of azotemia, and severe hepatic dysfunction heralded poor prognosis. At 15 days after receiving marrow transplant, despite signs of early engraftment (absolute neutrophil count 880 cells/Ul), the patient succumbed to multisystem organ failure. A postmortem examination demonstrated autolytic and congestive changes in liver, spleen and gastrointestinal tract, acute renal tubular necrosis, bone marrow showed no evidence of leukemia. Skin findings were consistent with acute graft-versus-host disease; T. gondii was not seen.

Most disseminated cases of toxoplasmosis in stem cell transplant recipients are diagnosed after death,² whereas in the case presented the patient had received appropriate antiparasitic therapy for a week and death probably resulted from systemic inflammatory response due to complicated engraftment syndrome. In allogeneic HSCT recipients, pleomorphic skin lesions may be due to various infectious and noninfectious causes. A comprehensive diagnostic approach including tissue samples of suspicious lesions may be critical in assessing care for these severely immunosuppressed patients.