A 36-year-old woman presented at our institution (Gachon University Gil Hospital) with erythematous confluent maculopatches on her face, trunk, and palms; jaundice; fatigue; pruritus; and aggravation of skin lesions over the previous week. She had been previously diagnosed as having erythema multiforme 2 weeks earlier at a private dermatology clinic and had also been administered dapsone with oral antihistamines (mequitazine and cetirizine) and topical corticosteroid for 8 months.\nOn admission, her vital signs were a blood pressure of 110/70 mm Hg, heart rate of 78 beats/min, respiratory rate of 18 breaths/min, and body temperature of 38.8℃. She reported no night sweats, loss of weight, or arthralgia. A physical examination conducted at presentation revealed bilateral, multiple enlarged lymph nodes on both sides of the neck with splenomegaly. All of the nodes were non-tender, firm, and measured 0.5 cm to 1.0 cm in diameter. Laboratory tests results were as follows: Hb 11.2 g/dL, white blood cell 13,070/mm3 (segmented neutrophils 24%, lymphocytes 66.3%, and eosinophils 0.1%), platelets 245,000/mm3, total bilirubin 5.4 mg/dL, direct bilirubin 3.8 mg/dL, aspartate aminotransferase/alanine aminotransferase (AST/ALT) 233/366 U/L, lactate dehydrogenase 1,610 IU/L (normal range, 200 to 485 IU/L), and an international normalized ratio of 1.25. She was negative for hepatitis B surface antigen, anti-hepatitis C virus Ab, and anti-human immunodeficiency Ab, but positive for hepatitis B surface antibody; and positive for anti-nuclear Ab, but negative for rheumatoid factor, anti-neutrophil cytoplasmic Ab, anti-Ro (SS-A, B) Ab, and anti-smith Ab. Serology tests showed no evidence of active Epstein-Barr virus (EBV) infection and no bacterial growth was found during a blood culture study. There was no hypergammaglobulinemia.\nAn excisional biopsy of a 1.0 cm cervical node showed diffuse polymorphic lymphoid hyperplasia with effacement of the normal architecture and abundant high endothelial venules; the cellular infiltrate was polymorphic, with abundant transformed lymphocytes and plasma cells (). Sinuses were frequently recognizable, but reactive germinal centers were not found.\nImmunohistochemically, the majority of infiltrating atypical lymphocytes were CD3+ T-cells (), and some activated large cells were reactive for CD30 (). Follicular dendritic cell meshworks expressing CD21 were expanded (), and infiltrating atypical T-cells were negative for CD10, BCL-6, and EBV by in situ hybridization. For a definitive diagnosis, a molecular study on the rearrangement of the T-cell receptor (TCR)-gamma gene was performed and showed polyclonality (). An IgH gene rearrangement study also showed polyclonality.\nAn abdomino-pelvic computed tomography (CT) scan revealed splenomegaly (14 cm), an enlarged portocaval lymph node (1.7 cm), and gallbladder wall edema (). No evidence of lymphomatous involvement was found by chest CT or a bone marrow trephine biopsy.\nBecause aggravation of the skin eruption persisted and the liver function test remained abnormal, the possibility of DHS (exfoliative dermatitis, acute hepatitis, and multiple lymphadenopathy) was raised. The findings of a transjugular liver biopsy were compatible with drug-induced hepatitis manifesting as granulomatous inflammation (). No evidence of lymphomatous hepatic involvement was found. In view of her skin lesions, medication history, and age, we concluded that the cervical lymphadenopathy was actually pseudolymphoma. Accordingly, low dose prednisolone (30 mg/day) per os was started after transjugular liver biopsy to relieve the dapsone-induced skin lesions and hepatitis. Gradually, the skin lesions improved and the cervical lymph node enlargement regressed. Her total bilirubin, AST, and ALT values also normalized after 3 weeks of prednisolone, which was then tapered over a month. Follow-up CT scans conducted 3 and 6 months after presentation showed that the size of the cervical lymph nodes and spleen had normalized, and produced no other findings suggestive of lymphoma progression ().
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.