Clinical Images: A treatable cause of bilateral leg edema and pleural effusion: yellow nail syndrome with IgG4-related disease

Abstract

The patient, a 78-year-old man with bronchiectasis and recurrent bronchial infections, presented with dyspnea persisting for 3 months. Physical examination revealed decreased right-sided breath sounds, marked bilateral pitting edema of the lower extremities, (A) thickened yellow nails, and submandibular gland swelling. Laboratory test results were unremarkable except for elevated serum IgG and IgG4 concentrations (1,766 and 563 mg/dL; reference ranges: 870–1,700 and 11–121 mg/dL, respectively). Potassium hydroxide and bacterial culture results were negative, ruling out nail infection. (B) Chest x-ray and computed tomography scan showed a right pleural effusion, which was an exudate with lymphocytic predominance, no malignant cells, and negative findings for bacteria or mycobacteria. Echocardiography confirmed normal cardiac function. Lymphoscintigraphy demonstrated delayed lymphatic transport and dermal backflow, consistent with lymphedema. Yellow nail syndrome (YNS) was diagnosed based on the triad of yellow nails, lymphedema, and pulmonary disease. (C) Pleural biopsy revealed lymphoid follicles surrounded by numerous IgG4-positive plasma cells with an IgG4/IgG ratio of 90%. Therefore, IgG4-related disease was identified as the underlying cause of YNS. The patient did not respond to diuretics but showed significant improvement with oral prednisolone (0.6 mg/kg) and compression therapy. At 6- and 12-month follow-ups, pleural effusion resolved, nails normalized, and lymphedema improved. YNS is a rare disorder associated with various malignancies or autoimmune diseases.^{1, 2} However, the etiology of the yellow nails in this disorder is not presently understood. Long-term prognosis depends on the severity of recurrent pleural effusion and underlying etiology.³ Although supportive care remains the primary approach in YNS management, recognizing IgG4-related disease as a treatable underlying disease is crucial for optimal patient care.