Immunoglobulin G4-related disease presenting with Raynaud’s phenomenon

Abstract

Immunoglobulin G4-related disease (IgG4-RD) is a systemic inflammatory disease characterized by elevated serum IgG4 and infiltration of IgG4-positive plasma cells in multiple organs, including the salivary glands, orbital adnexal structures, pancreas, kidneys, retroperitoneum, and skin (1). IgG4-RD presents with various symptoms based on the affected organs. However, Raynaud’s phenomenon is a rarely reported symptom. We herein report a case of IgG4-RD presenting with Raynaud’s phenomenon and digital ulcers. A 55-year-old Japanese man presented with repeated white and cyanotic changes in his fingers. Three months prior to his visit, a sensation of facial puffiness was noted. Two weeks prior to admission, Raynaud’s phenomenon was noted. His medical history included hypertension, asthma, and chronic sinusitis. He was taking telmisartan and inhaled budesonide/formoterol. On physical examination, his blood pressure was 146/70 mmHg, pulse rate was 88 beats/min, respiratory rate was 16 breaths/ min, and temperature was 36.8°C. He was alert and conscious. His bilateral lachrymal and submandibular glands were swollen. His right axillary and right inguinal lymph nodes were enlarged and palpable. His fingertips were cyanotic (Figure 1). Skin sclerosis was not observed in his fingers or forearms. The neurological examination results were normal. Laboratory findings showed that the complete blood cell count, electrolyte panel, and serum chemistry were normal. Serum IgG and IgG4 levels were elevated to 3855 mg/dL and 1420 mg/dL, respectively. The erythrocyte sedimentation rate was 99 mm/h and the C-reactive protein level was 0.62 mg/dL. Anti-nuclear antibody, rheumatoid factor, anti-neutrophil cytoplasmic antibodies, and cryoglobulin were negative. Computed tomography showed diffuse pansinusitis with mucosal thickening; multiple lymphadenopathies in the cervical, axillary, and mediastinal areas; swelling of the infraorbital and femoral nerve; intrapelvic nodules; and enlargement of the infraorbital canal (Figure 2). Submandibular gland biopsy and histological findings showed diffuse lymphoplasmacytic infiltration with fibrosis. Immunohistochemical staining against IgG4 demonstrated multiple IgG4-positive cells and IgG4/IgG-positive plasma cell ratio > 90%. Axillary lymph-node biopsy showed dense lymphoplasmacytic infiltration and an IgG4/IgG-positive plasma cell ratio > 50%. Treatment with oral prednisolone at 40 mg/ day (0.6 mg/kg/day) was initiated and tapered. His lachrymal and submandibular gland swelling improved, but Raynaud’s phenomenon did not. Two months after treatment, when he was taking prednisolone at 30 mg/day, digital ulcers developed at the tip of his fingers. We added 40 mg/day nifedipine and 60 mg/day sildenafil. The digital ulcers improved, but Raynaud’s phenomenon persisted. The serum IgG and IgG4 levels were still high, at 1559 mg/dL and 469 mg/dL, respectively. We increased the dose of prednisolone to 40 mg/day and added methotrexate at 8 mg/week. Raynaud’s phenomenon waned, and the serum IgG and IgG4 levels decreased to 768 mg/dL and 184 mg/dL, respectively. We gradually tapered the dose of prednisolone to 7.5 mg/day, increased methotrexate to 16 mg/week, and added azathioprine at 125 mg/day. Three years following treatment, the patient has not experienced a relapse of IgG4-RD symptoms, and has had no new symptoms or laboratory findings suggesting other rheumatological diseases. This study was performed in accordance with the Declaration of Helsinki, and written, signed informed consent was obtained from the patient. The clinical course of this patient suggests that Raynaud’s phenomenon can occur in IgG4-RD patients. Raynaud’s phenomenon indicates involvement of small-sized peripheral arteries and is commonly