The patient’s disease was already very advanced when the diagnosis was determined, and a hazardous complication was developing as well. A 63-year-old woman presented with a 2-month history of symmetrical violaceous swelling of the face (Figure 1A). Faint violaceous patches also marked her neck, upper chest, upper back, and both arms (Figure 1B). In addition, she had been suffering from a sore throat for the previous 3 weeks, and on the day prior to admission, she developed an intermittent fever. One month earlier, physicians at a local hospital arrived at a possible diagnosis of dermatomyositis, based on the patient’s clinical presentation and on skin biopsy results that showed interface dermatitis. They prescribed topical and oral steroids, but no improvement ensued. She visited our hospital for a second opinion and was admitted so that her symptoms could be further investigated.
Assessment
A physical examination revealed an ulcer on the patient’s left tonsil (Figure 1C). An otolaryngologist conducted a thorough work-up and found no evidence of a nasopharyngeal tumor or other abnormality. No proximal muscle weakness was identified, and electromyography showed no signs of myositis.
Initial laboratory tests disclosed mild transaminitis with an aspartate aminotransferase level of 43 U/L (normal, ≤34) and an alanine transaminase level of 47 U/L (normal, ≤36). The lactate dehydrogenase level was elevated at 445 U/L (normal, 135-260 U/L). Tests for antinuclear antibody, anti-Jo-1, rheumatoid factor, and anti-double-stranded DNA all produced negative results. Levels of creatine kinase, myoglobin, and C3 and C4 were within normal limits. A complete blood count demonstrated normocytic anemia with a hemoglobin measure of 11.8 g/dL (normal, 12-16 g/dL) and a mean corpuscular volume of 82.1 fL (normal, 80-100 fL). Thrombocytopenia was confirmed by a platelet count of 63,000 cells/μL (normal, 150,000-400,000 cells/μL).
The complete blood count was repeated the next day. Results included mild leukopenia with a white blood cell count of 3200 cells/μL (normal, 3500-11,000 cells/μL) and many atypical lymphocytes (22%). The patient’s platelet count had decreased to 49,000 cells/μL.
Based on the clinical and laboratory findings, the differential diagnosis included infection, autoimmune diseases, and lymphoproliferative disorders. The initial suspected diagnosis of dermatomyositis was questionable because the patient lacked the pathognomonic Gottron’s papules or Gottron’s sign. Whole-body computed tomography showed no obvious lymph node enlargement, but splenomegaly was noted.
Tests for antistreptolysin O, Epstein-Barr virus antibody to viral capsid antigen immunoglobulin (Ig)M, cytomegalovirus IgM, human immunodeficiency virus antigen/antibody, hepatitis B surface antigen, hepatitis C virus antibody, and herpes simplex virus IgM were negative or returned results within normal limits. However, tests for Epstein-Barr virus antibody to viral capsid antigen IgG, cytomegalovirus IgG, hepatitis B surface antibody, and hepatitis B core antibody were positive. Interestingly, Epstein-Barr virus DNA (79,743 copies/mL) was detected in the patient’s plasma by quantitative polymerase chain reaction.
The deeply indurated skin lesions on the patient’s cheeks suggested panniculitis. On the third day of hospitalization, we repeated the skin biopsy using a sample from her left cheek. Our goal was to confirm a tentative diagnosis of lupus panniculitis while ruling out subcutaneous evidence of lymphoma.
Diagnosis
On the fourth day of admission, laboratory testing indicated that leukopenia (white blood cells, 1900 cells/μL), thrombocytopenia (platelets, 46,000 cells/μL), and atypical lymphocytosis (26%) had advanced. Hepatitis and coagulation abnormalities had worsened, too. The patient’s lactate dehydrogenase level was 926 U/L; activated partial thromboplastin time was 44.5 seconds (control, 29 seconds); and D-dimer measured 3468 ng/mL fibrinogen equivalent units (normal, ≤500 fibrinogen equivalent units). Although her procalcitonin level was low at 0.33 ng/mL, and sepsis was not likely, we prescribed intravenous cefepime for prophylaxis.
The laboratory results shifted our diagnosis toward subcutaneous lymphoma, and this, combined with the finding of positive Epstein-Barr virus DNA in the plasma, indicated that the patient might have concurrent hemophagocytic lymphohistiocytosis.1 We then checked the patient’s serum ferritin level, and it was exceedingly high (10,619 ng/mL), supporting our concern for hemophagocytic lymphohistiocytosis. Because delayed treatment results in high mortality, we immediately administered parenteral methylprednisolone (prednisolone equivalent dosage: 1 mg/kg/day) and ordered a bone marrow biopsy. Ultimately, the pathology report from the bone marrow biopsy revealed hemophagocytosis without lymphomatous involvement.
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-Shih-Jyun Yang, MD, Chau Yee Ng, MD, Chih-Hsun Yang, MD, Pei-Hsuan Lu, MD
This article originally appeared in the June 2017 issue of The American Journal of Medicine.
