IMAJ • VOL 12 • JANUARY 2010 Case Communications

A Dramatic Response to Intravenous Immunoglobulin in a Patient with Mixed Cryoglobulinemia Ofer Almog MD, Tatiana Berlin MD, Pnina Rotman-Pikielny MD and Yair Levy MD

Department of Medicine E, Meir Medical Center, Kfar Saba, and Sackler Faculty of Medicine, Tel Aviv University, Ramat Aviv, Israel

tions of MC including cryoglobulinemic 1.2 mg/dl with proteinuria of 1 g per 24 Key words: intravenous immunoglobulin, nephropathy, skin ulcers, sensory motor hours. A kidney biopsy revealed focal cryoglobulinemia, , and widespread , glomerulonephritis. In addition, the pa- neuropathy, vasculitis high dose steroids with or without cyclo- tient had epigastric pain. A gastroscopy IMAJ 2010; 12: 53–54 phosphamide should be administered. A revealed non-specific acute gastritis promising new treatment for MC, which without signs of vasculitis. has not yet been studied in large-scale A 6 month course of cyclophospha- clinical trials, is intravenous immuno- mide therapy was initiated, combined For Editorial see page 45 globulin therapy. with high dose prednisone. Each attempt ryoglobulins are immunoglobulins We describe the successful case of a at tapering the steroids was followed by C that precipitate when cooled to less female patient with mixed cryoglobulin- reappearance of , abdominal than 37oC and dissolve when rewarmed. emia related to non-, who dem- pain, and urinary sediment. The high Mixed cryoglobulinemia type II is an onstrated a dramatic response to IVIG dose steroid treatment took its toll with autoimmune disorder comprised of cir- after high dose steroids and cyclophos- manifestations of osteoporosis, myopathy, culating cryoglobulins of both polyclonal phamide provided only partial relief. and water retention. IgG and a monoclonal IgM rheumatoid In 2003, the patient presented with factor that are directed against the IgG. myalgia and right arm , as well Type II MC causes small vessel vas- Patient Description as purpura on her limbs. An electromyo- culitis. The clinical manifestations of In 1996, a 34 year old woman presented gram revealed neural damage indicative type II MC include skin (60–100%), with purpuric rash and epigastric abdom- of mononeuritis multiplex of the ulnar peripheral nerve (20–90%), / inal pain. No diagnosis was made at nerve. Because these new symptoms arthritis (20–90%), renal (33–55%) and the time, and she was discharged on a 3 appeared while she was receiving a high gastrointestinal involvement (< 20%) [1]. month course of low dose steroids with dose of steroids, a clinical decision was Other common features are fatigue and full relief of her symptoms. made to initiate IVIG treatment (2 g/kg Raynaud’s syndrome. In 2001, the patient’s purpura recur- body weight). with is re- red with the addition of arthralgia. Blood The response to this new treatment sponsible for up to 90% of all type II MC analysis for immunoglobulins provided was dramatic. After only one course of cases. Because of its major etiological the diagnosis of mixed cryoglobulinemia. IVIG, the disease went into full remis- role in type II MC, eradication of HCV While testing negative for HCV antibod- sion, including disappearance of abdomi- by antiviral medications is a main treat- ies, her IgM nal pain, arthralgia, purpura, and kidney ment goal for this disorder. Another goal were positive. An elevated C-reactive pro- dysfunction. Cumulatively, the patient of treatment is symptom related and tar- tein and erythrocyte sedimentation rate received 10 monthly courses of IVIG. gets the autoimmune process. While no were also noted. The patient was treated One year after the last course of IVIG treatment is required for asymptomatic with low dose prednisone augmented she remained in remission, receiving patients, low dose steroids are adminis- later by , leading to remis- only low dose prednisone (5 mg on alter- tered to patients with mild to moderate sion. nate days). cryoglobulinemic syndromes such as In 2002, the patient presented with purpura, arthralgia, or peripheral sen- purpura on her limbs, deterioration of sory neuropathy. With severe manifesta- her kidney function, and hematuria. Comment Her creatinine levels rose from 0.8 to IVIG has come into increasing use in Ig = immunoglobulin

MC = mixed cryoglobulinemia patients with autoimmune and systemic HCV = hepatitis C virus IVIG = intravenous inflammatory diseases [2]. Of special

53 Case Communications IMAJ • VOL 12 • JANUARY 2010

interest is the favorable effect of IVIG simultaneously with steroids as first prolonged period. It is important to note in vasculitic peripheral neuropathy. Our therapy in a male patient with cryo- that the patient had failed to respond to group has demonstrated the beneficial globulinemic polyneuropathy, had a conventional treatment, which included effect of IVIG in autoimmune diseases beneficial effect. and high dose ste- in open-label clinical studies [3,4]. We The precise mechanism of action roids. We conclude that IVIG therapy described six patients with various auto- of IVIG in the treatment of autoim- may be a reasonable treatment in MC, immune/inflammatory diseases (Sjögren’s mune diseases and vasculitides is still especially when other modes of therapy syndrome, systemic erythematosus, largely unknown. A few possibilities have failed. vaccination-induced vasculitis, Churg- have been suggested including anti- Strauss vasculitis, ), all with idiotype antibodies, down-regulation Correspondence: Dr. Y. Levy vasculitic peripheral neuropathy. The of autoantibody synthesis, inhibition of Dept. of Medicine E, Meir Medical Center, patients were treated with high dose complement-mediated tissue damage, Kfar Saba 44821 Israel IVIG (2 g/kg body weight) and followed blockade of Fc receptors on phagocytic Phone: (972-9) 747-2592 Fax: (972-9) 744-0085 for 1–5 years after this treatment. In four cells, inhibition of complement activa- email: [email protected] patients – those with Sjögren’s syndrome, tion, down-regulation of T and Churg-Strauss vasculitis, SLE, and vacci- function, anti-cytokine effect, neutra- References nation-induced vasculitis – the neuropa- lization and enhanced clearance of end- 1. Monti G, Galli M, Invernizzi F, et al. thy resolved after IVIG treatment. Thus, ogenous pathogenic autoantibodies, and Cryoglobulinemia: a multi-centre study of the we believe that IVIG may be beneficial neutralization of bacterial toxins and early clinical and laboratory manifestations of primary and secondary disease. GISC. Italian

in cases of resistant vasculitic peripheral super-antigens. Group for the Study of Cryoglobulinaemias. Q J neuropathy and that IVIG should prob- IVIG therapy is usually safer than Med 1995; 88: 115-26. ably be considered as either a sole or an immunosuppressive agents but still 2. Pyne D, Ehrenstein M, Morris V. The therapeutic uses of intravenous immunoglobulins in auto- adjuvant treatment for patients with con- has possible adverse effects. These con- immune rheumatic diseases. Rheumatology traindications to conventional treatment, sist of skin rash, headache, arthralgia, (Oxford) 2002; 41: 367-74. or alternatively, for patients in whom anaphylactic hypersensitivity (espe- 3. Levy Y, Sherer Y, Ahmed A, et al. A study of 20 conventional treatment has failed. cially in IgA-deficient patients), renal SLE patients with intravenous immunoglobulin – clinical and serologic response. Lupus 1999; 8: The use of IVIG in MC type II has dysfunction, and possibly thrombotic 705-12. been reported without favorable effect. events. 4. Levy Y, Sherer Y, George J, et al. Serologic and In two case reports the IVIG treatment To the best of our knowledge our clinical response to treatment of and associated led to cryoglobulinemia (cryoglobu- report is the first to describe a patient with intravenous immunoglobulin. Int Arch linemic vasculitis) [5]; while in another with MC type II whose dermatologic, Allergy Immunol 1999; 119: 231-8. report, IVIG therapy, which was started nephrologic, gastrointestinal and neu- 5. Odum J, D'Costa D, Freeth M, Taylor D, Smith N, MacWhannell A. Cryoglobulinaemic vasculitis rologic symptoms were resolved almost caused by intravenous immunoglobulin treat- SLE = systemic lupus erythematosus completely with IVIG therapy and for a ment. Nephrol Dial Transplant 2001; 16: 403-6.

Capsule

An innervative small RNA involved in ALS

Amyotrophic lateral sclerosis (ALS) is a relentless disease ALS, and when this RNA was removed from mice by genetic characterized by progressive degeneration of motor neurons manipulation, the disease progressed at a faster rate. The that control muscle movement, leading to muscle atrophy salutary effects of miR-206 appear to be mediated through and paralysis. Williams and colleagues show that a small a signaling pathway in muscle cells involving histone deac- non-coding RNA that is selectively expressed in skeletal etylase 4 and a fibroblast growth factor modulator, activation muscle, miR-206, senses motor neuron injury or loss and of which leads to release of factors that promote nerve- helps ameliorate resultant muscle damage by promoting muscle interactions. regeneration of neuromuscular synapses. Expression of Science 2009; 326: 1549 miR-206 was dramatically induced in a mouse model of Eitan Israeli

“The 10 commandments are not a multiple choice” Anonymous

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