In a previously healthy older adult, a generalized rash gave way to an elusive diagnosis. Six weeks before the present hospitalization and after a period of sun exposure, this 65-year-old woman developed a pruritic rash on her arms, legs, and trunk that spared her face, palms, and soles. Shortly thereafter, the rash was followed by quotidian low-grade fevers to 100°F, together with malaise, cough, and sore throat.
Several primary care and dermatology evaluations followed over the next few weeks. Skin biopsy yielded histologic evidence of a superficial and deep perivascular dermatitis that improved minimally after a week of 20 mg of oral daily prednisone treatment. An initial admission to an outside hospital resulted in a diagnosis of community-acquired pneumonia and infectious mononucleosis on the basis of pulmonary infiltrates, lymphadenopathy, elevated liver function tests, and positive Epstein-Barr virus serologies. She was discharged with home oxygen therapy. However, given the persistence of her rash and fever, she was admitted to the Johns Hopkins Hospital for further care.
Assessment
Vital signs included a low-grade fever of 37.7°C (99.9°F), blood pressure of 115/61 mm Hg, heart rate of 104 beats/min, respiratory rate of 20 breaths/min, and oxygenation saturation of 95% on 4 L of oxygen via nasal cannula. Physical examination was notable for a diffuse erythematous, macular, morbilliform rash on her arms, legs, chest, and back that spared the face, palms, and soles. Notable additional findings were cervical and axillary lymphadenopathy, bibasilar inspiratory crackles, elevated jugular venous pressure to 12 cm of water, splenomegaly, and peripheral edema. Heart sounds were unremarkable. There was no evidence of joint swelling, mucositis, or alopecia.
Initial laboratory evaluation was notable for mild anemia (hemoglobin 11.7 g/dL). Total white blood cell (6.99 K/cu mm) and platelet (157 K/cu mm) counts were normal, but there was lymphopenia (absolute lymphocyte count 350 K/cu mm; normal range, 1.10-4.80) and an atypical lymphocytosis (12%). Peripheral blood smear noted atypical large granular lymphocytes. In addition, there was borderline hypercalcemia (corrected Ca 10.4 mg/dL) and mildly elevated lactate dehydrogenase (240 U/L; normal range, 122-220). Epstein-Barr virus studies revealed negative capsid antigen immunoglobulin-M, positive capsid and nuclear antigen immunoglobulin-G, and quantitative plasma polymerase chain reaction level of 13,500 copies/mL; these laboratory results were consistent with chronic Epstein-Barr virus infection.
Over the subsequent week, daily temperature fluctuations peaked from 37.8°C (100°F) to 38.7°C (101.7°F). Rheumatology, infectious disease, dermatology, and hematology services were consulted. Thereafter, extensive rheumatologic and infectious workup was unrevealing. However, computed tomography scan of the chest without contrast revealed bilateral pleural effusions, pulmonary infiltrates, mediastinal and axillary lymphadenopathy, and scattered pulmonary nodules. Bilateral lower-extremity Doppler ultrasound displayed a nonocclusive right femoral vein thrombus.
Next, whole-body positron emission tomography computed tomography scan was pursued to further evaluate the lymphadenopathy; this revealed diffuse hypermetabolic lymphadenopathy of the neck, axillae, mediastinum, retroperitoneum, and inguinal areas, as well as pulmonary consolidation with an extensive interstitial pattern suggestive of lymphangitic infiltration, pleural effusions, and a diffusely infiltrated spleen.
With concern for malignant serositis, a thoracentesis was performed, revealing a transudative pleural effusion by Light’s criteria (pleural fluid protein 2.7 g/dL and lactate dehydrogenase 78 U/L; serum protein 6.2 g/dL and lactate dehydrogenase 200 U/L; protein ratio 0.4; lactate dehydrogenase ratio 0.4). Cytopathology lacked malignant cells but was enriched in lymphocytes.
There was ongoing concern for a lymphoproliferative malignancy in light of the extensive lymphadenopathy and fever. However, consideration for an occult infection and an autoimmune inflammatory rheumatologic disorder remained.
Diagnosis
Thereafter, whole blood flow cytometry yielded evidence of a distinct population of lymphocytes displaying an unusual T-cell phenotype, as follows: CD3+ (dim); CD5+ (dim); CD7+ (dim), CD4+, and negative for CD26. Further, T cells accounted for 88% of the circulating lymphocytes. These findings were strongly suggestive of a circulating T-cell lymphoma.
Consequently, excision of an axillary lymph node was performed that demonstrated features of the hyaline vascular variant of Castleman’s disease, particularly small follicles with prominent interfollicular vascular proliferation. Staining for human herpesvirus 8 and Epstein–Barr virus was negative. Of note, effacement of normal follicular architecture within the lymph node was absent.
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-Samantha C. Shapiro, MD, Ibironke Oduyebo, MD, Rima Koka, MD, PhD, Allan C. Gelber, MD
This article originally appeared in the April 2016 issue of The American Journal of Medicine.
