UCLA Department of Medicine Clinical Insights

25yo non-verbal Asian male born with cerebral palsy with spastic quadriparesis, restrictive lung disease s/p chronic tracheostomy, GJ tube dependence was found on labs over several years to have leukocytosis (WBC 10-18), mild microcytic anemia (Hgb 10-12.8), and thrombocytosis (platelets 400-1000). Per his parents, patient appears to be comfortable and at his baseline mental state, denying fevers, cough, bleeding, urinary changes, diarrhea or signs of pain. Initial exam without lymphadenopathy, changes in cardiopulmonary status, abdominal changes, and without decubitus ulcers. Differential diagnosis at the time was indolent infections (ie atypical/fungal pneumonia, osteomyelitis), lymphoproliferative disorders, hematologic/bone marrow disorders, and autoimmune conditions. Additional labs showed elevated Erythrocyte Sedimentation Rate (ESR) >130, C-Reactive Protein (CRP) 7.3, IgA 473, IgG 3154. Iron levels were low. Peripheral blood smear with leukocytosis with few reactive lymphocytes, thrombocytosis and microcytic anemia. JAK2 mutation was negative, SPEP/Immunofixation was without monoclonal antibodies, TSH normal, Quantiferon-Gold negative, LDH normal. Repeat exam on follow up visit revealed signs of severe tophaceous gout on helix of the ear and multiple joints (bilateral wrists and bilateral ankles). There were also small, hard subcutaneous nodules on right forearm. Initial exam missed these signs because his hands and feet are chronically contracted and covered with clothing. Uric acid was 15.6, HLA-B*58:01 was negative. Father revealed he has gout too. Patient was started on allopurinol and colchicine (both crushed and given via G tube) after rheumatology consultation. 

On subsequent follow ups over the next four months, tophi on ear improved but tophi on right ankle got slightly worse, with increased skin ulceration (without infection), and new development of exposed yellow nodules on right forearm, indicating deposits of urate crystals. WBC 13.9, Hgb 11.8, platelets 673, uric acid 11.4, ESR 83, CRP 6.4. Allopurinol dose was increased several times and patient was advised to see Rheumatology for evaluation for partial response of disease vs refractory disease.

Gout is the most common form of inflammatory arthritis, affecting approximately 9.2 million adults in the United States (1). Synovial fluid analysis showing monosodium urate crystals under polarized light microscopy is the gold standard for diagnosis, but blood tests can also show neutrophilic leukocytosis and elevation of inflammatory markers (2). In this case, patient also had significant thrombocytosis and IgA and IgG elevations due to inflammation from gout. In a young patient such as this, it would also be prudent to consider secondary causes for gout.

Tophaecous gout is a form of advanced gout characterized by tophi, which are nodular deposits formed in joints and soft tissue comprised of monosodium urate crystals surrounded by multinucleated giant cells and an outside fibrovascular area. Tophi formation is a chronic granulomatous inflammatory response to urate crystals and takes years to develop. The most common sites of tophi are joints, helix of ear, olecranon bursa, finger pads and Achilles tendon. Classic inflammatory findings like erythema and even tenderness are not necessarily present. However tophaceous gout can lead to joint destruction and deformities. Bone erosions and skin ulcerations can also occur, as seen in this case. Infection is a risk at the site of skin breakdown and ulceration. In this patient, the yellow and white nodular deposits on the arm are representative of a high urate burden (3)

American College of Rheumatology recommends a treat-to-target strategy with urate-lowering therapies (ULT), with allopurinol as the preferred first line therapy, to maintain a serum urate level of <6 mg/dl (4). If a patient fails all standard therapies, refractory gout can be treated with IL-1 inhibitors and other therapies such as Pegloticase (5, 6). In cases of tophi causing complications (ie infections) or those at risk for permanent joint destruction, surgical intervention may be appropriate (7).