Cryocrystalglobulinemia as a cause of systemic vasculopathy and widespread erosive arthropathy

Abstract

This report describes the case of a woman who was admitted to the hospital for highly destructive axial and peripheral arthropathy in association with acute malignant hypertension and skin purpura. Type I IgGK serum cryoglobulinemia was identified and was classified as a monoclonal gammopathy of unknown significance. Cryoglobulin was shown to crystallize in the serum and synovium fluid and was responsible for both granulomatous microcrystalline synovial inflammation and occlusive vasculopathy in the kidneys and skin. Cryocrystalglobulinemia pathogenicity and therapeutic implications are discussed.Monoclonal immunoglobulins may crystallize within or adjacent to plasma cells, mostly in multiple myeloma (1). Localized crystal deposits independent of plasma cells have been seen in various tissues with differing degrees of organ failure, including skin, cornea, synovium, testes, thyroid, adrenal glands, spleen, liver, lungs, coronary and renal arteries, renal glomeruli, and tubules. We report a case of cryocrystalglobulinemia responsible for skin and renal vasculopathy and associated with highly erosive arthropathy involving both peripheral and axial joints. CASE REPORTClinical course and laboratory findings. The patient, a 45-year-old woman, presented with severe polyarthropathy and gave a history of pain dating back to 1991. She had pain in multiple joints including the distal and proximal interphalangeal joints, metacarpophalangeal joints, wrists, elbows, shoulders, cervical spine, sacroiliac joints, heels, ankles, and metatarsophalangeal joints, which caused progressive disability. At different times on subsequent examinations there was gross and sometimes pseudotumoral swelling of the tendon sheaths of the fingers, dorsum of the hands, and elbows, and considerable restriction of movement of all involved joints. There was no rash on the palms or soles, acne, psoriasis, subcutaneous nodules, tophi, lymphadenopathy, or enlargement of the spleen or liver. Hemography results were normal.The erythrocyte sedimentation rate was 120 mmhour. The C-reactive protein level ranged from 2 mg/dl to 4 mg/dl. Liver test results and lactate dehydrogenase and muscle enzyme levels were within normal ranges. The uric acid level was 200 pMAiter. The serum calcium level was 2.5 M A i t e r , and the phosphate level was 1.5 M l l i t e r . Findings of serologic studies for infectious agents, including Lyme borreliosis, human immunodeficiency virus, parvovirus B19, and hepatitis B and C were negative. The results of tests for autoantibodies, including rheumatoid factor, antinuclear antibodies, anti-DNA, antiextractable nuclear antigen, antiphospholipid antibodies, antineutrophil cytoplasmic antibodies, and direct Coombs' test were negative. Serum C3 and C4 complement components and CH50 values were within normal ranges. HLA class I typing was negative for B27. A monoclonal cryoprecipitable 1gGK gammopa-

Dangerous small B-cell clones

“…74 Rare forms of organized monoclonal immunoglobulin deposits related to type I cryoglobulins also include cryocrystalglobulinemia and so-called glomerulonephritis with organized microtubular monoclonal immunoglobulin deposits (GOMMID) ( Table 3). 75,76 These conditions are associated with various B-cell-derived immunoproliferative disorders, including chronic lymphocytic leukemia 76 and multiple myeloma. 77 The organized formations, crystals or microtubules, are present within the synthesizing B cells.…”

“…In addition to kidney involvement, patients with cryocrystalglobulinemia may have systemic vasculopathy (Figure 7) and widespread erosive arthropathy, mimicking rheumatoid arthritis. 75 Treatment is focused on the underlying B-cell neoplasia. Corticosteroids and removal of the monoclonal immunoglobulin by For personal use only.…”

Crystalglobulinemia with Fulminant Course with Cylinder-like Bodies on Peripheral Blood Smear

“…Crystalized immune globulin in patients with hypergammagloblinemia in various organs has been reported (Table). Among these, angiitis-like clinical manifestations in patients have been identified as crystalglobulinemia or cryocrystalglobulinemia (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14). In addition, patients found to have only crystal phagocytosis, renal crystal lesions, or corneal lesions have been diagnosed with crystal-storing histiocytosis (15), crystal nephropathy (16), and crystalline keratopathy, respectively (17).…”

“…The clinical manifestations of this condition differ depending on the organ in which crystal deposition occurs. Terms such as crystalglobulinemia (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14), crystal-storing histiocytosis (15), crystal nephropathy (16), and crystalline keratopathy (17) have been used. The clinical manifestations of crystalglobulinemia resemble those in patients with vasculitis or sepsis; namely, purpura, neuropathy, and multiple organ failure.…”

A Patient with Abnormal Kidney Function and a Monoclonal Light Chain in the Urine

“…The deposits are first categorized as organized versus nonorganized (25). The organized deposits are further classified as fibrils (AIg amyloidosis or monoclonal fibrillary GN), microtubules (immunotactoid GN or cryoglobulinemia), or crystals/inclusions (LCPT, crystal-storing histiocytosis, and cryocrystalglobulinemia) (26)(27)(28). Light-chain casts occasionally have a crystalline structure that fractures during processing of the tissue.…”