A 30-year-old woman presented to the hospital with a morbilliform and pruritic generalized rash [], along with high-grade fever, fatigue, and malaise for 4 days. Physical examination and blood tests revealed enlarged cervical and inguinal nodes, leukocytosis (up to 66,800 white blood cell/mm3), and elevated levels of hepatic transaminases, lactate dehydrogenase, ß-2 microglobulin, and erythrocyte sedimentation rate. Serology results for hepatitis, syphilis, typhoid fever, and brucella were negative. The whole body computed tomography showed multiple neck, chest, and abdominal lymphadenopathy with splenomegaly suggestive of lymphoma []. A skin biopsy specimen revealed epidermotropism of atypical lymphoid cells, with CD30 positive staining as well as a dense perivascular and perifollicular lymphoid infiltrate []. An excisional biopsy of a 1.0 cm cervical node showed diffuse polymorphic lymphoid hyperplasia with effacement of the normal architecture with strong and diffuse staining for CD30 on immunohistochemistry, positive anti-leukocyte common antigen, and high proliferation index (Ki67 80%). All findings were consistent with lymphoma. However, osteomedullary biopsy showed no evidence of lymphoproliferative disorder, was absent for immunomarkers and high eosinophils proliferation rate. T-cell receptor rearrangement studies on the skin, lymph node, and bone marrow biopsies, failed to detect monoclonality. A detailed review of her past medical history revealed that she was started on lamotrigine 50 mg/day for somatization disorder 40 days prior to the onset of symptoms. Blood samples were positive for human herpesvirus 6 DNA. The diagnosis of DIHS/DRESS was made; lamotrigine was discontinued and treatment with oral corticosteroids (prednisolone, 60 mg/day) was started with rapid tapering. The patient made a full recovery with no organ deficit on follow-up visits at 1, 2, 4, and 6 months.
An 18-year-old African American female with a history of hyperthyroidism presented to our facility with fever, chills, body aches, significant cervical lymphadenopathy, facial edema, and a progressive (eventually generalized) macular morbilliform rash. She reported that elevated transaminases had been noted during a recent visit with her endocrinologist. Her CBC included a WBC count of 8,600 mm3, hemoglobin of 12.4 g/dl (MCV 77.8 fL), and platelet count of 261,000 mm3. Ferritin was markedly elevated (1229.6 ng/mL); serum iron, TIBC, and iron saturation were decreased, suggestive of anemia of chronic disease. AST was elevated to 127 units/mL, and ALT was elevated to 239 units/mL. Hemoglobin electrophoresis revealed normal adult hemoglobin. A rapid HIV test was nonreactive. PCR testing of peripheral blood was negative for EBV and HHV-6. Multiple blood cultures were negative.\nAbdominal ultrasound showed splenomegaly and enlarged porta hepatis lymph nodes. A PET scan revealed diffuse hypermetabolic lymphadenopathy involving cervical, supraclavicular, axillary, pelvic, and inguinal nodes, as well as findings consistent with malignant infiltration of the bilateral kidneys and spleen (). Although the possibility of a drug reaction had been in the differential diagnosis prior to the imaging studies, the degree and extent of the imaging abnormalities raised clinical concern for a malignant process.\nDue to the concern for malignancy, axillary lymph node and bone marrow biopsies were performed. Examination of the bone marrow showed that it was appropriately cellular for age (∼80%), with maturing trilineage hematopoiesis, polyclonal plasmacytosis, and eosinophilia. Scattered small T-cell aggregates were present. Flow cytometric immunophenotyping did not detect any abnormal lymphoid populations. No evidence of malignancy was identified.\nHistologic examination of the lymph node revealed mostly preserved, but significantly distorted, nodal architecture with expansion of the paracortex by a mixed infiltrate of small lymphocytes, eosinophils, histiocytes, plasma cells, and scattered large atypical lymphoid cells, including occasional Reed–Sternberg-like cells. Secondary follicles were largely absent (Figures and ). A few apoptotic bodies and pigment-containing histiocytes were identified.\nImmunohistochemical stains for CD20, PAX5, CD79a, OCT2, and BOB-1 highlighted the B-cell population in the cortex that was largely confined to primary follicles. CD23 highlighted irregularly expanded follicular dendritic cell meshworks. CD3 highlighted numerous T cells in the paracortex and interfollicular areas. CD15 highlighted granulocytes. CD30 highlighted scattered large immunoblasts, including rare Reed–Sternberg-like cells (); no sheets of positive cells were seen. MUM1 was positive in plasma cells, predominantly in the medullary cords and sinuses. ALK immunostaining and EBV in situ hybridization (EBER) were negative.\nThe lymph node findings, including architectural distortion, expanded follicular dendritic cell meshworks, eosinophilic infiltrate, and proliferation of large CD30-positive lymphoid cells raised concern for a malignant process such as T-cell lymphoma or classic Hodgkin's lymphoma; however, the morphologic and immunophenotypic features were not entirely typical for those diagnoses. Molecular analysis of the lymph node did not detect any monoclonal IGH or IGK gene rearrangement or T-cell receptor gene rearrangement.\nTwo days after the lymph node biopsy was performed, the patient's WBC count had risen to 24,100/mm3. Examination of the peripheral blood smear revealed neutrophilia, atypical lymphocytes, and mild relative eosinophilia, with an increased absolute eosinophil count of 1,400/mm3. On further review of the patient's history, it was noted that the patient had received a course of minocycline to treat folliculitis, beginning approximately five weeks prior to admission and ending four days prior to admission.\nAfter consideration of all of the available information, a diagnosis of DIHS was made. The minocycline was discontinued permanently. Following treatment with prednisone, the patient's rash, leukocytosis, and lymphadenopathy gradually resolved.