MGUS: significant beyond hematology

Vanderschueren SW, Mylle M, Dierickx D et al. Monoclonal gammopathy of undetermined significance: significant beyong hematology. Mayo Clin Proc. 2009; 84:842-847.

MGUS is found in 3% of patients older than 50, 5% older than 70, in 7 % of patients seeking medical evaluation, and converts to myeloma at rate of one percent per year. Authors present five OTHER associations of MGUS that are commonly underrecognized.
1. Acquired C1 inhibitor deficiency. should be suspected in patients with repetitive often stereotypic episodes of angioedema, with no urticaria or pruritus or family history, & in pts with recurrent acute abdomen with normal CRP and low C4 levels. Hereditary form occurs in first two decades usually, acquired forms in elderly patients with MGUS in up to 40 % of cases (IgG, IgM or IgA). In acquired forms C1q levels are low due to consumption. Acute prophylaxis can be done with antifibrinolytics eg. transexamic acid or danazol, and acutely FFP has variable success.
2. Systemic capillary leak syndrome should be suspected in patients with repetitive hypovolemic shock, capillary leak and hemoconcentration (in case report, HB went from 15 to 23 in one day). Attacks characterized by prodrome malaise, fatigue, OH, polydipsia, palpebral edema, last 1 to several days and have high fluid requirements during an attack. MGUS usually IgG is typically present. Intestinal edema, ascites, muscular edema, pleural and pericardia effusions occur, may have compartment syndrome. Terbutaline, theophylline, and IVIG are used to treat.
3. Acquired von Willebrand syndrome-- uncommon condition occurs in elderly patietns with no history or family history of bleeding, with MGUS in 50-60 %. Desmopressin works transiently. High dose IVIG has been used. Suspect with mucocutaneous or postop bleeding.
4. Schnitzler syndrome-- heralded by repetitive fevers and chronic, initially nonpruritic urticaria. CRP and ESR are typically very high. MGUS is usually M type. Anakinra, an IL1 antagonist shows promise.
5. Scleromyxedema-- characterized by typical skin eruption and visceral or repetitive neurologic involvement. Case reported of 39 yo man with episodic confusion preceded by flu like illness proceeding to status epilepticus and prolonged postictal coma. Over weeks, appeared erythematous plaques on face and skin creases over glabella , confirmed with biopsy to be scleromyxedema. Tx was plasmapx, IVIG, dexamethasone, autologous stem cell, thalidomide. Its caused by hyaluronic acid deposition in superficial dermis and production of MGUS usually IgA. Also called papular mucinosis and generalized lichen myxedematosus. Occurs in patients usually 30-50 , may include MI as well. Also called dermatoneural syndrome.