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105 Generalized chronic urticaria secondary to zinc-containing insulin
105
GEMERALIZED CHRONICURTICARIA SECONDARYTO ZINCCONTAINING INSULIN. Kuo C. Chang, V.D., John A.
Galloway, M.D., Robert Miles-Lawrence, M.D. and Stephen Adelman, M.D., Portland, Oregon and Indianapolis, Indiana A 54 year old oriental female diabetic developed late local swelling 4 days after the initiation of daily USP beef insulin lente injection. In the 6 months following a switch to purified pork lente, the reaction to insulin gradually changed from late local swelling to satellite hives near the site of injection, and finally to generalized chronic urticaria. The initiation of daily purified pork protamine sodium insulin (PSI) injection resulted in the disappearance of chronic urticaria in 2 days. In the subsequent 2 years, urticaria recurred when PSI was 'replace2 with : (1) purified pork lente (twice): (2) recombinant DNA human insulin isophane sus$;i& (containing zinc); and (3) the mixture of zinc sulfate (2 ug per unit of No urticaria appeared when insulin) and PSI. the patient took zinc sulfate 220 mg b.i.d. p.o. for 2 weeks along with the PSI injection. Skin tests to zinc-containing pork or beef purified insulins failed to elicit immediate, late, RASTs to beef, pork, or delayed reactions. human insulins and protamine (courtesy of Philip F1.D.) were also negative. In this Fireman, patient, the product of zinc and insulin interaction during preparation is a likely cause of chronic urticaria which is not apparently IgE mediated.
108
106
and&&&&&~+&&, La Jolla, Ca. The camp lete evaluation of recurrent angloedema requfres the exclusfon of HAE and acquired Cl Inh deficiency. The serum C4 concentration is usual I y but not necasSac I ly decreased In HAE. We have eva I uated a mare sensitive assay for C4 actlvatlon (the ratlo of C4d to C4 determined by rocket imun~noeIectrophoresIs1 fn HAE and acquired Clfnh def Ic lency. Group 1 consisted of 52 samples from 20 patients wlth HAE and 5 with acquired When possible, samples were Cl inh def Iclency. obtained both w fth the patlent on as wel I as off Group 2 consisted of 27 patlents with therapy. Idiopathic urticarIa/angIoedema, and group 3 conslsted of 7 normal volunleers. C2, C4 and Clinh concentrations as well as C4d/C4 ra?iOS were determined for each sample. The C4d/C4 ratios were signlf[cntly elevated (p<.OOOl) in group 1 compared l’o groups 2 and 3. C2,C4 and Cllnh were also sigiffcantly decreased in group 1. 7 of the 52 samp ies In group 1 had a normal C4, however al I 52 samples showed an Five of the 27 pallents e 1evated C4d/C4 ratio. In group 2 exhibited an elevafed C4d/CQ ratio lndlcatlve of complement activation, None Of the normals In group 3 had elevated CWC4 Therefore the C4d/C4 ratio Is a ratios. sensltlve though not speclflc marker for HAE and acqu lred Cl Inh def iclency, and a normal C4d/C4 ratio can be consldered to exclude HAE and acquired Cl inh def Iciency.
J.&j&&&la Jolla, Ca. HAE and AC10 are characterized by low Ctlnh We stud fed complement and and ang loedema. contact system activation In induced blister fluids and plasmas from patlents wlth HAE, AClD Inh or norma I s. Cls-Cl inh and kal I Ikreln-Cl complexes were measured by ELISA In excess purif led normal Cl inh (to complex free proThe complement and contact systems were tease). activated l,~ m by heat aggregated gamma globul In or kaol In with excess Cl Inh to determine maximum generatable protease-Cl tnh complex. EibibC HAE (11) AClD (4) Norm. (4)
nn280 3.482* 0.670* 1.097
= (95) (87) (64)
-
9p280 ,722” .512 .405
&.l.N
= (41) (94) (28)
(.3%) .006 ,248 (34) w* .026 ,027 ( 5) AClD (4) (( .;;; ,001 ( 1) .008 Norm.(4) (* = slgnlficant with p < ,051 These studies show that the camp lement and contact systess are both actfvated In blister flulds from HAE patients whereas only complement In AClD the bl lster was activated In plasma. fluids contained Cls-Cl Inh but not kal IlkrelnThe concentrat Ions of Cl sCl Inh complexes. Cllnh complexes in the blister fiulds and p lasmas of patients w Ith AC10 were near max Imal. These differences between HAE and AClD suggest that the biochemical consequences of Cllnh deficiency In these disorders are different.
131
GEMERALIZED CHRONICURTICARIA SECONDARYTO ZINCCONTAINING INSULIN. Kuo C. Chang, V.D., John A.
Galloway, M.D., Robert Miles-Lawrence, M.D. and Stephen Adelman, M.D., Portland, Oregon and Indianapolis, Indiana A 54 year old oriental female diabetic developed late local swelling 4 days after the initiation of daily USP beef insulin lente injection. In the 6 months following a switch to purified pork lente, the reaction to insulin gradually changed from late local swelling to satellite hives near the site of injection, and finally to generalized chronic urticaria. The initiation of daily purified pork protamine sodium insulin (PSI) injection resulted in the disappearance of chronic urticaria in 2 days. In the subsequent 2 years, urticaria recurred when PSI was 'replace2 with : (1) purified pork lente (twice): (2) recombinant DNA human insulin isophane sus$;i& (containing zinc); and (3) the mixture of zinc sulfate (2 ug per unit of No urticaria appeared when insulin) and PSI. the patient took zinc sulfate 220 mg b.i.d. p.o. for 2 weeks along with the PSI injection. Skin tests to zinc-containing pork or beef purified insulins failed to elicit immediate, late, RASTs to beef, pork, or delayed reactions. human insulins and protamine (courtesy of Philip F1.D.) were also negative. In this Fireman, patient, the product of zinc and insulin interaction during preparation is a likely cause of chronic urticaria which is not apparently IgE mediated.
108
106
and&&&&&~+&&, La Jolla, Ca. The camp lete evaluation of recurrent angloedema requfres the exclusfon of HAE and acquired Cl Inh deficiency. The serum C4 concentration is usual I y but not necasSac I ly decreased In HAE. We have eva I uated a mare sensitive assay for C4 actlvatlon (the ratlo of C4d to C4 determined by rocket imun~noeIectrophoresIs1 fn HAE and acquired Clfnh def Ic lency. Group 1 consisted of 52 samples from 20 patients wlth HAE and 5 with acquired When possible, samples were Cl inh def Iclency. obtained both w fth the patlent on as wel I as off Group 2 consisted of 27 patlents with therapy. Idiopathic urticarIa/angIoedema, and group 3 conslsted of 7 normal volunleers. C2, C4 and Clinh concentrations as well as C4d/C4 ra?iOS were determined for each sample. The C4d/C4 ratios were signlf[cntly elevated (p<.OOOl) in group 1 compared l’o groups 2 and 3. C2,C4 and Cllnh were also sigiffcantly decreased in group 1. 7 of the 52 samp ies In group 1 had a normal C4, however al I 52 samples showed an Five of the 27 pallents e 1evated C4d/C4 ratio. In group 2 exhibited an elevafed C4d/CQ ratio lndlcatlve of complement activation, None Of the normals In group 3 had elevated CWC4 Therefore the C4d/C4 ratio Is a ratios. sensltlve though not speclflc marker for HAE and acqu lred Cl Inh def iclency, and a normal C4d/C4 ratio can be consldered to exclude HAE and acquired Cl inh def Iciency.
J.&j&&&la Jolla, Ca. HAE and AC10 are characterized by low Ctlnh We stud fed complement and and ang loedema. contact system activation In induced blister fluids and plasmas from patlents wlth HAE, AClD Inh or norma I s. Cls-Cl inh and kal I Ikreln-Cl complexes were measured by ELISA In excess purif led normal Cl inh (to complex free proThe complement and contact systems were tease). activated l,~ m by heat aggregated gamma globul In or kaol In with excess Cl Inh to determine maximum generatable protease-Cl tnh complex. EibibC HAE (11) AClD (4) Norm. (4)
nn280 3.482* 0.670* 1.097
= (95) (87) (64)
-
9p280 ,722” .512 .405
&.l.N
= (41) (94) (28)
(.3%) .006 ,248 (34) w* .026 ,027 ( 5) AClD (4) (( .;;; ,001 ( 1) .008 Norm.(4) (* = slgnlficant with p < ,051 These studies show that the camp lement and contact systess are both actfvated In blister flulds from HAE patients whereas only complement In AClD the bl lster was activated In plasma. fluids contained Cls-Cl Inh but not kal IlkrelnThe concentrat Ions of Cl sCl Inh complexes. Cllnh complexes in the blister fiulds and p lasmas of patients w Ith AC10 were near max Imal. These differences between HAE and AClD suggest that the biochemical consequences of Cllnh deficiency In these disorders are different.
131