A 47-year-old man presented to the clinic reporting color changes on fingertips, initially pale fingers, followed by blue discoloration and numbness. He denied photosensitivity, oral ulcers, skin changes, cough, dyspnea, gastrointestinal symptoms, or urinary changes. Medical history was remarkable for recurrent superficial venous thrombosis of the left leg treated with rivaroxaban.
Physical examination revealed pale fingers with hypertrichosis without puffy fingers, sclerodactyly, telangiectasia, digital ulcers, or calcinosis cutis. No hepatosplenomegaly or lymphadenopathy was present. Initial laboratory studies showed elevated platelets (479 × 109/L, reference value 150–450) with normal hemoglobin concentration (15.3 g/dL, reference value 11.5–15.5), hematocrit levels (44%, reference value 41–50), acute phase reactants (ESR and CRP), thyroid-stimulating hormone (TSH), clotting profile (PT and TPT), creatinine, and B12 vitamin levels. ANA were positive at 1:320 titers in a speckled pattern. Tests for extractable nuclear antigen (ENA), anti-dsDNA titers, complement, antiphospholipid antibodies, cryoglobulins, antineutrophil cytoplasmic antibody (ANCA) by direct immunofluorescence, and nailfold capillaroscopy were unremarkable. Therefore, a diagnosis of secondary Raynaud’s phenomenon was made, treatment with acetylsalicylic acid was initiated.
Twenty-four months later, the patient had paraparesis due to symmetric sensorimotor demyelinating polyneuropathy, and he was diagnosed with Guillain–Barre syndrome. Intravenous gammaglobulin (IVIg) was initiated at 0.4 g/kg/ day for five days, with an incomplete response. Raynaud’s phenomenon persisted, associated with acrocyanosis, hypertrichosis, and white nails (Fig. 1a, b). Additional laboratory test results were received, and ANA was positive but with a different pattern (1:1280 in a nucleolar pattern); serum protein electrophoresis revealed a polyclonal gammopathy with a monoclonal (M)-protein on immunofixation (IgG lambda), and increased concentrations of VEGF (827 pg/mL, reference value 31–86 pg/mL). 24-h urine protein measurement was 130 mg of protein per day (reference value: less than 150 mg per day), and a radiographic bone survey did not reveal sclerotic bone lesions. Another nailfold capillaroscopy was unremarkable, and tests for ENA and antiphospholipid antibodies were normal.
The Rheumatology staff proposed amyloidosis as a differential diagnosis due to the identification of monoclonal gammopathy and peripheral neuropathy. However, the patient did not have autonomic neuropathy, which may be present in 15% of patients with AL amyloidosis. Entrapment neuropathies such as carpal tunnel syndrome are frequent, but this manifestation was absent in our patient. Skin manifestations in amyloidosis are periorbital purpura, waxy thickening, macroglossia, and subcutaneous nodules. Nevertheless, a few cases with Raynaud’s syndrome have been described [6].
Another differential diagnosis proposed was type I cryoglobulinemia which frequently can occur with Raynaud’s phenomenon and peripheral neuropathy. In our case, the patient had demyelinating polyneuropathy compared to cryoglobulinemia, which occurs with sensory-motor axonal polyneuropathy. Other peripheral nervous system manifestations of cryoglobulinemia include small-fiber polyneuropathy and mononeuritis multiplex [7].
Based on the initial presence of superficial venous thrombosis, thrombocytosis, Raynaud’s phenomenon, hypertrichosis, white nails, acrocyanosis, and with the onset of demyelinating peripheral neuropathy, monoclonal gammopathy, and elevated levels of VEGF, the patient was diagnosed with POEMS syndrome by the Hematology group.
The bone marrow showed megakaryocytic hyperplasia and increased atypical plasma cells by 5 percent. Treatment with lenalidomide and dexamethasone was initiated, with the improvement of Raynaud’s phenomenon, acrocyanosis, and white nails. The patient showed neurologic partial response after 6 months and required a walker brace and physical therapy for mobility (Fig. 2). Autologous hematopoietic cell transplantation was proposed, pending authorization by the patient.