Annual Review

c~lcarly that tllc nwmal skin can withstand il fairly st,rong acid solution (3N H(I1, f,H 2.0). 011 tht? oth(~t~ hand, iI.lkilli of l)II 12.6 (~YOIII a WITI- Ijarative standpoint, considerabl;\- mcqkcr as alkali than 3N HCl is as acid) usually produced a reaction. (Solutions were in contap with the skin for about twenty-four hours).

Along the same lines as the work discussed above, Blank4 has studied the reaction of the skin to patch t-es& with various fatt,y acids. The lest persons included a group with normal skin, a group with a clinical his- tory of soap-irritability, and a group of patients with atoljic dermatitis or contact-type dermatitis. In normal personss. t,he saturated fatty acids of low molecular weight produced a much greater number of reactions than did those of high molecular weight. In the groups wit,h skin dis- ease, this difference was still present, although the total number OF r(‘- actions was much greater.

Further study of the reaction of the skin t.o i’atty acids on skin sites moistened repeatedly with buffer solutions of varying pH indicated that “the amount- of alkali which must be added before a fatty acid becomes an irritant increases with the increasing molecular weight of the acid. ”

These experiments indicate that the harmful effects of soap are prob- ably governed bg the combination of at least two factors which may bc synergistic : the effect of the fatty acid on the skin, and the reaction of the skin to alkali. There is as yet., however, no universal agreement on t,his subject. Previous studies, such as those of Jordan, Walker, and Osborne,” and of Goldman,j have indicated that allergic hypersensitivit) may sometimes play a part. True allergic hypersensitivity to soaps a.pparently is comparatively infrequent. Certainly, patch tests with undiluted soaps are not to he recommended in investigating eczematous eruptions in which soap is thought to play a part. A suspension of from 1 to 5 per cent soap in water is usually a suitable dilution for patch test- ing.

Studies of the experimental sensitization of man and animals hare continued during the past J-ear. Landsteiner and Chase6 have studied further the problem raised by Strauss and Coca.’ It will be recalled that the latter authors demonstrat,ed that, if a monkey was sensitized to poison iv?- by application of t,hc extract to the skin of an arm, the sensi- tivity became general. If, however, a cuff the full thickness of the skin were first turned down on the arm, the hypersensitivity did not spread past the gap in the continuity of the skin. By applying poison ivy extract to an island of skin on the guinea pig, Landsteiner and Chase demonstrated that the hypersensitivity failed to become general only if the incision was deep enough to sever the lymphatics beneath the skin. Incision through the skin alone was not sufficient to prevent the spread. The authors conclude that free lymph circulation beneath the skin is necessary for the spread of the sensitization.

410 THE: JOURXAI, OF ALLERGY

The variability of the process of sensitization has also been pointed out by Simon and I~otspeich.ll Scnsitivi@ did not derclop in all persons on whose skin a concentrated poison ivy extract was applied. some were entirely resistant,. Of further interest is the finding that palch tests with serial dilutions of poison ivy extract, done before and after a series of intramuscular injections of concentrated extract, rcvc&~l no appreciable alteration of the degree of h\-persensitivity. The authors found, in addition, that three commonly used treat,ments for acute contact dermatitis caused by poison iv\- (calamine lotion, 5 per cent potassium permanganate solut,ion, and 5 per cent lead acetate solution) a.ppeared t,o he without influence upon the clinical course of the disease.

Zisserman and Birch”;’ hare contributed a new study on t,he possible effectiveness of poison ivy injections in bot,h the prophylaxis and trcat- ment of poison ivy dermatitis. Nothing could more strongly emphasize t,he present uncertain st,atus convcrning the usefulness of spcvific measures in the prophylaxis of plant dermatitis. The aut.hors first briefly review some of the l)revious st,udios. Without analyzing 111~ variability of the extracts and met.hods used, or the variables of type and amount of clinical exposure, season of the year, age of patients, previous susceptibility, incidence of previous attacks, etc., the results as prescntcd in the brief historical review were approximately as follows :

The following are among the authol*s who have reported favorable results from administration of extracts in the specific t~c~tv1~1 ol’ iq dermatitis : Strickler, Williams and i\lac(:rcgor, Biaings, Clock, (iowen. Sharlit, and Canlfeild.

The following are among t.hose who have rcl)ortcd 110 beneficial vfY’t,ets of extracts used in specific twtrtnrmt : Kmusc and Wcidman, ( ‘orson, and Sompeyrac.

Among others, the following have rck)ortetl t,lle specific extracts t.o bc effective in prophyZn~% of poison ivy dvrmat,itis : Clock, (:owa.n, Bla.nk and Coca, Biederman, Canlfeild, and Molitch and Poliakoff (t,wo re- ports).

On the other hand, there arc some authors who report that specific injections are of no proph~~lnctic 1duc. Thcsc include Bachman and, now, 2Zsserma.n and Birch, with a controlled study on a group of 1,731 boys. Moreover, the unpublished study of Greenberg and Mallozzi, per- formed at the clinic of one of the rcricaw\-crs scvc~ral yars ago, inrluded a group of workn~s at a Civilian (lonservation Corps camp. In these also no striking or general prophvlactic effcc~t could bc demolt- strated following t,he specific injections. The incidence of iry dermatitis in the injected group (seventy-seven men) was only very slightly less than in a control group (forty-t,wo men) nndcr approximately identical conditions of subsequent clinical oxl)osrlrc.

These wide diverpenccs in results require cxplanat ion and stud\-. for the problem is of theoretic and praclical importance far transcending

ihc immcdiat c suhjcct of poison ivy dermatitis. The question involved is simply : (-‘an t,hv itllcrgic scnsit ivitp in contact-type eczcmatous derma- titis he materially rcdnced or ;~bolished by sl)ecific measures; and do or do not the results in iv\- dt~rnlillitis indicate tllilt physicians will some da\- be able, throlqyh sl)cvific JIIWS~IW, t,o prevent or materially reduce the inc~idence of allergic colitavt-lypi‘ deimat it is in general, including the literally hundreds of thousands of uses due to the many thousands of different oc~lll);ltion;ll ant1 c~str;rocciil)atiolial c~czematogenous al- lcrgens?

The following arr among the questions now awaiting solution : Are t,hr divcqqant results drlc IO the use of diffcrcnt~ cstraets Y’ 018 to different, dosage? 01’ to diRerent routes of ildministratiorl ? Or to differences in degrcv of the subsequent osposurcs to thr cscitant on the part oi the treated individual 7 ()r to illly other known favtors f ( )I’ to mistakes and technical C~~OI’S? ()r to (‘(~l.tilill \-ariables n-hivh arc’ as yet entirel! beyond our knowledge P

Allergic contact-i>-l)e tlermal it is is ~~robabl~ the most common of all allergic discascs of Ulilll. It seems, 1 ticrefore, that no snbjevt in allergy alld dcrmatolog)- is of g~'l~~rt(~l~ sigllifi~at1c.c or morv l~rgentl~- in need of further careful study.

Shelmirc12 has reported ir1stwnct.s of contact-t~.pe detmat itis ljroduced by weeds and has described a mrthod for preparing extracts of weeds for patch testing. In over 10,000 control tests with these extracts, onl~ four mildly posit ivc reac~t ions wore folmd.

In the light of Shclmire’s work, it seems almost certain that dermn- tologists must from timt to time scv and fail to recognize cont,act-type dermatitis caused by weeds. Eslra~ts of ~cds, prcparcd by Shelmire ‘s m&hod, should bc available for clinical USC. When these extracts arc available. the incidence of sucah contarl tlcrmatitis may well be found lo bc high, especially in rural ;II'CilS.

The increasing use of rotcnone (the active ingredient of derris and cube) in insect and plant, sprays indicates that it too map beeomc (OK may already be) RI1 important PiYlllSC! of contact dermatitis. In t,liis con- nection it is of interest that liacouchot” has described an eruption oc- curring in all workers coming in contact with powdered cube roots in a factory in which a rotcnone inssccl- spray was being manufact,ured. The eruption was limited to the rcyion of the ~ (renitals. I-nfortunately, no mention is made of patch tests. and the qlleslion of allergy is not dis- cussed. The rircumstancc>s of this industrial dermatitis are such that one must, sasped that it, is allergic until the contrary is demonstrated.

A general consideration of industrial dermatoses (the most import,ant of which is contact-type dermatitis) has been published by Strandberg ilIld asso&tes.‘4 LL Especially recommended in this group of papers are Bonnrvie’s discussion of the etiology and pathogenesis of contact derma- litis and Bostriim’s discussion of the patch test.

412 THE JOURNAL OF ALLERGY

BeringI” has suggested a classification of industrial dermatitis, divid- ing these skin diseases into three groups : 1. Dermatitis, which includes eruptions which result from local irritant (toxic) action. These erup- tions do not tend to spread. 2. Dermatoses which depend upon the exhaustion of the defense mechanisms of the skin (Abnutzung). An example of a dermatosis belonging to this group is c.ement eczema. 3. Allergic contact-type dermatitis.

It appears questionable whether these three mechanisms are at Ihe basis of all the various forms of eczematous reactions. And it seems almost impossible to follow Bering’s proposal to limit the use of the word eczema to allergic contact-type dermatitis. However, we are in skm- pathy with attempts to clarify the problems of industrial dermatitis b> better classification, based as far as possible upon pathogenesis. It seems to us that some confusion has resulted in the past and still results from the use of the term “contact, dermatitis.” This expression most often refers to allergic contact-type dermatit,is, even though t,he word “aller- gic” is omitted. However, there are many instances of nonallergic dermatitis produced by contact with chemicals and other substances. These eruptions must not be confused with the allergic eruptions. Until some better classification is in general use, care must be taken to qualify the term ’ ‘ contact-type dermatitis, ” so that there shall be no confusion between allergic and nonallergic eruptions.

Mention must be made here of the review by Flandin and his collabora- tor@. I7 of 1,000 cases of industrial dermatitis. While no new view- points are presented, nonetheless, the statistical study of these cases merits the attention of all physicians who have a special interest in industrial dermatitis.

An interesting and new industrial contact-type dermatitis has been reported by Watrous.18 Four persons working for the first time with nicotinic acid, developed within an hour or so an erythematous maculo- papular eruption, with itching and burning. Other workers failed to develop the eruption under similar conditions. While the author states that the pathogenesis of this eruption is unexplained, it seems probable t,hat it is not the usual alle@c contact-type dermatitis. The short time between exposure and eruption makes one suspect that the reaction was urticarial in nature, that the symptoms might have been produced by transepidermal penetration of the nicotinic acid. However, unt,il further studies are done, this explanation remains pure hypothesis.

Ziindel and Jentsch,l’ studying the occupational eczema of bakers, found that allergic hypersensitivity to cereals and to persulfate forms the basis for practically all the cases of this dermatosis. Hyper- sensitivity to persulfate (by patch test) was found to underlie the acute eczematous eruptions, while hypersensitivity to cereals (by intracutane- ous test) was found in association with the infiltrated and lichenified

eruptions. These two allergic h!-pcrsensitivitics were fo~mcl to IIC itI- dcpcndent, ol’ one anot,her.

kibeau and lTkraincazyk2” have discussed the dcrmatzitis of 1;7unclrrssc~s.

Jwinting orlt t,hat the Javellc xvatcr commonl,v used by thaw INxsol~s in I~‘r~~nw is a solut,ion of sodium hypochloritc with potassium bic~hromat (1 ;rtldctl as a stabilizer. Thrse investigators found in their j);rtients cvi- tl<~nco of a double scnsitirit!- to chlorine as 7~11 as to c~tiromatv.

In the rt9Gx-crs1 cspcriencc, lis[)el,sensitiril!- to chromate is commoll. brit contact li~l)clrsc’llsiti~it~ to chlorine its slich is estrcmc~l~- rare, il’ it vsisis at all. (V’hilc the role of c.hloi.inc-c.onlairlili g c~m11wunds in pi’o- tlticing acncform eruptions ma)- bc allergic ii) natnre~ it cT1’tiliIll~~ is not

contact-type dermatitis of the si~me variety as c~liromatc dermatitis. i !Yv

are not prepred to accept the conclusions of tlicw authors ii1 regard to

c~hlorinc unt,il this question has been stndicd i’nrt her, in l)art iv&r v;il h rc~ferencc to the inflnenw of the alkali ~)rcsent in Jnrelle natcll~.

T hc pwcctltion of industrial derm;~titis, including allw$ic~ CW~~~~C- t>.lw clermatitis, has rcceivcd partic~ulw attention in the past few years. ,111 cxcellcnt~ summar!- of rcwnt advances in this field will tw found ii) 1 hc> paper by Klauder, Cross, and Brow11.‘~

Thtx n(‘w federal regulations coverinK foods, drugs, and c*~smct ivs 11iL\.c Iwcn rcriewcd recentI\- by ICluml)l).2” The requirements fog’ labcling will now nlijk(a it. possible for the ph,wicinn to dctcrminc much mow wsil) thail formerly which ingredient of a proprietary remedy may have ~irust~tl the contact-type dermatitis which his patient prcwnts. l’ill.il

~~llen~lcnediaminc and thca para rod dyes ((dolor Index So. 44) have bccw c~liminatcd from cosmcties. It is unfortunate that, the 1imit;ltioiis of

0111’ knowledge of t hc allcrgie rwct ions to organic dyes ~~~wlutlc :I JI~O~T

t Iwro~7~l1 cwnsidcr;~t ion of t hc al Icyic l)roblcms associated wit lr the use ol’ vosmct its. Noncthelrss, the new regulations are a great ~1~1) fonvarcl.

()~rc must admit that if wcrv s7~hstance which collld lwssibly srnsitizc~

\z(~ffl~’ c~liminatcd from cwsm~fies, ycry little. if ali\-t tiing, woultl Jw Icft !

,\mong the drugs indispensable to ph>-sicinns and also amon? t how \vllich scnsitizc fairly freclucntly arc the local anesthetics. Ilollandc~P’

rwcntly reported an instance of allergic contact-type dermatitis from ~~o11towinc. 111 an interesting stud>., I\I. H. ( 1oodman”4 rclwrts that his

l)ill icnt with c~ontacl-t\-iw clermatit is ])rodLlcctl 1);. procaaincl showed jwsi- 1 ive patch 1 csts to all JJil ra-an1inohcnzoatc anesthetics; in fwt, there w~~r~~

lwsit ivcl tests to anilin and to salts of ~,a~~a-~lminob(~nzoic witl. On I II(~ oihc~r hand, there wwv nrpatiw palch tests to bc~nzol. to salts of 019 ho-

;rncl rn(~ln-amillol)cnzoi~ acids, to alypin (henzoic acid dvri\-al iv(x). ant1 to

local anesthetics of the quinolin and c*oca.inc groups.

In this caw there was a definite c~orwlation oI’ vhcmiwl st rnvi ~~(1 ail(l 11?-l)c,i~sc~nsili~it!-. Olwrv;1tions of the wvicvcrs clrlrin:: lhv I)ilSl i’(w

)-(‘iIt’s ilrtlic7ifc th;lt. in TIliln)- inslalrc~c’s Of 11:.-l)c~i.sc,ilsiti~ii~. to lo(*;ll :lJl(‘v-

414 THE JOURNAL OF ilLLERGY

thetics, this correlation either is not, present or is considerably more ob- scure than in the patient studied by M. H. (Goodman. Further studies of this sort will be of considerable interest.

Jordan’s”” report of contact-t,ype dermatitis from opium derivatives, as well as that of l~arnb’” concernin g quinine dermatitis following the ingestion of anacin, are of interest. The latter report serves as a re- minder that allergic contact-type dermatitis may develop as a result of t,he ingestion or injection of a drug. The allergen in such cases is dis- tributed hematogenously and reaches the shock tissue (epidermis) from within rather than from without. In these instances, patch test.s with the drug are positive (contrary to the usual drug eruption, in which, as a general rule, all skin t,ests arc negat,ive). Outstanding among the causes in our cases of contact-type dermatitis from within are quinine, chloral hydrate, and mercury. (The fact that this form of dermatitis can be elicited also from within has impelled us to use the term “contact- type dermatitis ’ ’ rather than “ contact dermatitis. ’ ‘)

The report of Levison and Harrison2’ of dermatitis following injec- tions of theelin is interesting and unusual. The reviewers believe, how- ever, that the investigation of this case did not prove conclusively that the hormone was the cause of the eruption.

The report of MaddenZs on reactions in tattoos includes one case in which the red (cinnabar) portion of a tattoo was swollen and slight,ly itchy. This patient showed positive patch tests to mercury compounds. Previous authors, including Ballin, and the reviewers have observed similar cases, in which mercury hypersensit,ivity apparently developed several years after t,he tattoo had been completed. In these instances, too, the red portions became swollen and in some instances developed ulcers. (This rare eventuality ma?; be of some significance in relation to Hol- lander’s recently developed method of cinnabar t,attooing in t,he treat- ment of prurit,us ani or vulvae.)

The report of Bernsteine” of dermatitis callsed by a sulfur-meat ram- plex is another instance of an eruption produced by sensitivity to a combination of two substances, neither of which alone is capable of elicit- ing the reaction. (Compare cable-splicers’ dermatitis reported by Schwartz and Hacker and discussed in the 1937 review.)

Among the miscellaneous papers dealing with allergic contact-t,yye dermatitis which remain for consideration, mention must he made of Bechet’s30 warning regarding the generalized eruptions which may some- times result from patch tests, particularly when applied in a faulty fashion. Another danger, that of patch testing with an improper con- centration of a substance, has been reduced, at least for the substances commonly used in testing, by t,he publication of the list of Rostenberg and Sulzberger.“l For over 700 substances this list gives the concentra- tion and vehicle to be used in performing the patch test. It is hoped

416 THE JOURNAL OF ALLERGY

IJippard38 studied the immunologic responses of normal and eczematous infants to egg white and to milk. Forty normal infants who had nevcl caten egg showed no skin reaction (urticarial) to egg white. Twent,J- infants who had been fed cooked e gg showed only one positive comple- ment fixation to egg white. After the administrat,ion of raw egg white, however, five of nine cases showed a positive intracutaneous test ant1 complement fixation. On the other hand, ten of twenty-one infants with eczema showed a positive urticarial reaction to egg white, although the! had never been fed egg. Of sixteen eczcmatous babies who had been fed small amounts of egg, fifteen showed a positive skin test. Both the normal and the eczema group showed reactions (at least complement fixation) to milk. These reactions were transitory in the normal infants.

The findings presented in this study arc, on the whole, confirmatory of the so-called “ Schloss phenomenon. ’ ‘W Normal infants go through a phase of sensitivity to new allergens. IJnlike the atopic person the normal individual has few manifestations of this allergic hypersensitivilj which is soon lost (immunization?). The atopic person, on the other hand, becomes sensitive and stays sensitive for an abnormal length of t,ime. He fails to become immunized to the new exposures at the normal rate or in the normal manner. But the evidence presented by Lippard would indicate that, the atopic baby, in addition, beco?lzes sensitive moor easily. This may be true for infants but, as Simon and Rackemann4” have demonstrated, it is not true for adults, at least as regards certain selected allergens.

Clein41 has studied the first allergic manifestations in infants. Eighty- two of 100 allergic infant,s developed a rash on the face as the first allergic manifestation. It is of intcrcst that twenty-one of this group of 100 developed allergic symptoms while still on t,he breast,. All but t,hree of these cases cleared up when cert,ain foods were eliminated from the mother’s diet,.

Feinbergl” has discussed t,he role of inhalant, allergens, garticu1arl.v pollens, in seasonal atopic dermatitis. His conclusions agree with thosr generallv accepted that pollens are important factors in this diseases. In the reviewers’ experience, it is cstremcly rarely that pollens arc apparently the only or the one major factor in atopic dermat,itis, evr11 in cases with very apparent seasonal exacerbations. I:nfortunatcly fol* the allergic approach, in adult, or adolescent persons with at,opic dcrma- titis, the ctiological factors are often exceedingly numerous.

Layman and Gumming+“’ have reported that at,opic dermatitis bias influenced relatively littlc by histaminase given over a period of from one to t,wo months. In eight cases which these authors studied t,here was no improvement which c*ould be att,ributed to the use of hist’aminase. This finding is disappointing. for a reliable means of relieving lhc

GOODIvLtX ASD SIJLZRERGER : ~\I,I,F:R(;\- IN DERMATOI~O(;Y 417

418 THE JOLJRXAL OP ALLERGY

Important contributions are t 1~0s~~ of Harq- Kaglc and his collabora- tors, and of Sherman, Stull, and Haml)ton.4SJ These investigators demon- strated that, the serum of guinea pigs sensitized by injection of alum- precipitated pollen toxoid contained a subst.anee which would produce passive sensitization of human skin. This power to sensitize passively was transit,ory.

Kahn”” has reported what is apparently a most unusual o~nrrence- an acneform eruption from the nasal applicat,ion of pollen in a hay fcvel patient. Shortly after the application, there vvas itching, burning, red- ness, and swelling of one cheek. T,ater acneform lesions appeared.

The dermatologist not, infrequently sees acneform eruptions associated with it,ching. In rare inst,ances the acne lesions start as whcals. The case reported by Kahn should enrourage the attempt, to discover a specific allergen when itching is a 1)rominent feat,ure of an iWIlCfol’rr1

dermatosis. In some such cases foods a,nd other allergens may set as “trigger factors” ; and such cxcitants can even produce exacerbations of acne vulgaris. It is, however, to be rccallrd that in all these casts there is no evidence of atopy, and skin tests are generally nsrless in attempting to discover the clinically culpable allergens.

The ‘ ‘ erythema of .I he ninth day ” of Milian is a type of arsphenamine reaction which merits the attention recently given it by Cafiizarcs and

Thomas.“’ In a study of eleven caascs of this eruption, the authors found that, in most instances, arsenical drugs could be administered wit,hout reaction after the disappearance of the eruption. Three patients were given further arsphenamine without reaction even hefore the eruption had disappeared. In two of the elrvcn cases, further arsphenaminc was not tolerated. In general, the best, procedure is to interrupt. treat- ment until the skin is clear and then to resume it cautiously. The mecha- nism of such erupt,ions remains obscure. The explanation proposed by Milian (the activation of a virus such as that of measles) merits further st,udy but is by no means generally accepted as yet.

(:olz”* has reported an instance of hypersensitivity to both trivalent and pentavalent arsenical drugs. Several months after developing an exfoliative dermatitis from neoarsphenamine, the pat,ient was given one injertion of tryparsamide. Within four hours after the injection, the first signs of a recurrence of the exfoliat,ive dermat,itis appeared.

A sensitivity such as this one is rare. This report serves t,o emphasize the fact that there is considerable variation from patient to patient in arsphenamine dermatitis. Sometimes the sensitivity is directed toward

420 THE JOURXAL OF ALLERGY

animals. The evidence indicates, however, that at least a large number of human drug eruptions are allergic. Further than that it is im- possible to go at the present time.

‘hm~‘P has produced fa,irly convincin g evidence of the presence of protective antibodies in the serum of rabbits infected with syphilis. These antibodies can be demonstrated about six months after infection. Mixtures of tissue emulsion from rabbit chancres and of serum from rabbits infected with an homologous strain of spirochetes are incubated at 37” C. and then inoculated into previously uninfected animals. X comparison of the lesion resultin, w from the inoculation of this mixture and the lesion resulting from the inoculation of a mixture of the same emulsion with normal rabbit strum demonstrated quite clearly that the serum from the infected animals contained spirocheticidal antibodies. This conclusion was reached because of the later appearance of the lesions which resulted from the inoculation of t,he immune mixt,ure, the decreased size of the lesions, and in some instances, the complete absence of lesions.

This contribution is of import,ance as a direct demonstration of circu- lating antibodies in cxpcrimental syphilis. The controversy between Chesney and Kollc (referred to previously in these reviews) was eon- cerned with the nature of the change in reactivity which appears after infection wit,h syphilis. While these two investigators were in accord as far as experimental data were concerned, their interpretation of these data differed. Chesney maintained that there was a true immunity in syphilis; Kolle, that there was no true immunity, but only a state which he referred to as “ chancre-immunity. ” Tf Turner’s work is accepted, there can be no further disagreement, on this point, for the demonstration of circulating antibodies is incontrovertible evidence of true, even though incomplete, immunit,y.

BcckeP’ has confirmed observations previously made by Eagle”’ OII t,he antigenicity of flocculate obtained from the serum of patients wit11 syphilis. While this work is by no means as direct and fundamental an observation as that of Turner, ncverthelcss, it offers additional suppori to the proponents of true immunity in syphilis.

The Frei test has come to be generally accepted as a specific reaction. It is of interest that the intravenous injection of 0.1 C.C. of the mouse brain antigen (prepared from the brains of mice infected wit,h lympho- granuloma inguinale) gives a typical febrile response in patients who have had lymphogranuloma inguinale. Decker, Caiiizares, and Reider”’ found this test to be specific and useful as a confirmation of the skin test.

Franchic has studied the histology of the positive Frei test in eom- parison to the histology of nodular reactions to other antigens (strepto- coccus, staphylococcus, etc.). Only in the positive Frei test was there

a tobwculoid strLtet11re. This st.1tcl>~ again eml)ltasizcs the fact: that SUM)- staltccs 0t her thall the tubcrclc bacillus or its lipoids can prod17cc il 1 nbcrcnloid trpc of reaction.

Iieint and Wak~4eld’;~ have reported an interesting vase of flaccid pai~aplcpia following a diagnostic intdcrmal injwtion of E’rti ant igtw. Iicac4ions of this sort ltavc been rcpor1cd lo follow ittjwtions of ot~lwr rmrclatod s1tbs1anws. It is not linown tlcfinitcly 1 hat stlvh react ions arc allergic. The inc1tbalion lwriod (in I his (~a~, clc\-cn days) gives sul)port lo thaw who bclicvc) Ihal. a11 allergic ~wclion is in ihc~ bavk- ground.

,\mort~ 1.h rtrwt~~ rcccnl~ skitt lcsts ill’(’ I hose for cvltittocowal discasch and for cwcidioidal y*anulorna. Rose and (lulbc~~tson”” have drscrilwcl a skin lest whielt is bclicved to bc spwific* for ec~hinocowus infcct~ion. Kessel”” has described a skin reaction of the tulwr~ulin type (twent)-- four lo forly-eight ho117,) to wwidioi<lin, ()f twchnty-six patients \\,itlt pr~ve(1 infwtiott with (‘c~~dioidrs im~~ilis, twcttt)--two showetl a posi- 1 ivr tttbcrc.11lin-t!I,c skin r(L:tc+ic,lt. The four patients \\-ho hat1 no w- avtio7ts wcw in the actvanced stages of the disease (possibly attrrgica). ‘I’hc twults of cxtctisivc~ c~onirol twts ittdicate 1 hat Ihis wadott is spwific. ~Jawl~sott”~ has rrpot~tetl gootl results froltt the specific it~rtttuttiz;ttion \vitlt eocciclioidin.

~2lldersoll ant1 Stolics’~” have stntlicd the 17sr of staphylococcus tosoicl and umbot,osoid (losoid ~)lns vacciitr) in frmttt~ulosis, acne vulgaris, and other resistant pyogvnic* tlermatosc~s. JIost inicrcsting from the imm17no- logic standpoint is tltv i’avl that, just as reported by Snlzberger and (I. RLI~~II, the elinicxl rcwtlt did not I)itrall(‘l the ittcrcasc in staphylo- ~w~cus antitoxin titer of the blood.

This finding is an csamplt~ of a wttdiliot~ \vhich obt,uins in various skin tlisea.scs. The factor ol’ the immmte state of the skin itself often ;lIll)~ill’S t0 1X! Of gW;lt?l illl~~Oidilll~c~ 1 hall the !)lY’sc’llW 01’ at)scncc ot c~irculating antibodies. Hasi ha17scw”!’ has l~c~rforrnctl an ingenious cs- Iwimcnl~ designed to clcmonsttx~~~ the indrpcttdcnw of the skirt in 11tv prod17ction of ststtsitivit y. Thor g:rwups of fiftwtr persons wwc injected with horse ser1tnt iii tltiw different xva?3. (Iroup I twcived 0.1 c.(x. in- 11*avcnously: Group) II twciwtl 0.1 C.C. irttracntatteousl!- ott i.hc Icft fort- arm: and (4ro1ip I I I rrwivc(l tcrt subc1ttancous ittjrctions of a 1 :lO dilu- lion of ltorw sct~m in \-arious scalterrd sites. ;Utw fourteen days all sltbjects were tested by tltv injection of 0.1 c.c. each of three horse sernm tlil17tions (10, 1, and 0.1 pet’ celtl) in the right, upper arm. I11 Group 1

only three persons sltowed skin reactions lo the test injections. The prr- sons in Gronps TI and III showed more frequent and mow intense sensi- tivity than Ihose in Gronp T.

Thcrc is a large body of older esperintental work wlticah indicat,cs that I hr skin has considerable indcpendencc in alletyic statw.’ The pari,

412 THE JOURKAL OF ALLERGY

l)layed by the skin in originating and in modifying allergy is oA,cn ovc‘r- looked. Haxthausen’s work emphasizes once more the import,ance 01 Ihe allergic state of the skin as contrasted to t hc g(~ncral allergic state of the individual.

Considerable interest has been manifested in the past few \-ears in the patch test with t’uberculin as a substitute for the Piryuct or Mantous test. Vollmcr and Goldberger;” hare carried out a comparat,ive st,ndJ of the Mantoux test and the patch test on 678 children, of whom 261 were known to have active tuberculosis. This st,udy was, in general, con- firmatory of these authors’ prcvions invcstigat,ion, which was discussed in last year’s review. Their most recent work indicates that the patch test has 100 per cent reliability us comparcd to the intradermal test with the first strength of purified protein dcrivativc and better than ‘3’3 pel cent reliability when compared with second strength P.P.D. Court:’ and others have likewise found the tuberculin patch test reliable.

In our discussion last year it was pointed out that there was still much to learn about the tuberculin patch test. The same ran be said at this writing. An investigation of the histologic charaetcristics of the reaction will be of considerable interest.

A series of papers which discuss various aspects of erythema nodosum7’ leaves one with a conclusion which has been expressed before in these reviews : that erythema nodosum is a symptom complex and not an independent disease ent,ity. In the papers cited above, there is some difference of opinion in regard t,o the cause of this eruption. A few! such as Rabeau and Ukrainczyk, find it to be of tuberculous origin. The undeniable fact that, eq-thema nodosum may be part of rheumatic in- fection, tularemia, gonococcus infection, l~mphogranuloma inguinale, infection wit,h Cocci&ides is)anaitis, etc., or that it may be a drug erup- tion makes it impossible for the reviewers to consider it a tuberculous disease. In some clinical groups luberculosis is undoubtedly a common cause of eryt,hema nodosum; but it is by no means the only cause of this eruption.

Allergic aspects of fungous infections have received comparatively little attention during the past year. However, among the many case reports which have appeared in the literature is one which merits par- ticular attention. Wiesmann7” investigated a patient with a lichenoid trichophytid. In the skin as well as in t,he enlarged regional lymph nodes, mycelial threads could be demonstrated. Cultures of material taken from the glands were negative. The author believes that the cultures were negative because the organisms were either weakened or killed by the allergic reaction which they aroused.

In general, the demonstration of fungi in the lesion of the epidermo- phyt,id erup’tion or in lymph nodes or blood of patients who present such

So&w pH, the Hwction to Ointments aml Wohtions of Difiermt 1~11 ~111 tlw E:ffwt of tile Skin in Modifying tht plI of Applirtl Solutions, ,hcl~. I)mn:ct. di Syph. 39: "5:: l'J::!).

4. Blank, 1. H.: ,~c?icm of d:tp on tllr Skin , ~\Wll. I)rrm:rt. & Sypl1. 39: x11, 19:w. -5. .Jorclan. .J. \\:.. \V:tlker. Il. I,.. an<1 Osborne. F;. I). : Studies in the bhrrnatizinr

Stu,l;s, .J. Inwit. l)&rrat. 2: Sl, 19::‘). 111. Snlzherger, >I. B., ant1 liostc~nl)rly, -1.. .Jr. : ~\cyuire(l Specifica Bupwsensitivit~

(Allrrgy) to Sinrplv (!liemids: IV, A Rlrtlio(l of Experimental Sensitization : ant1 lhnon,str:~tion of In~reaw~l Suweptil,ility in Intlivi.clu:dr \\‘itll Ec~zrrnatou~ Ihwn;~titis of Contact Typr, J. ln~n~unol. 36: 1 T, I!)::‘).

11. Simon, F. A., an11 r.0t+p+h. E. : Srnritivity to I’oison I\-?. .J. In\-&. Dermat. 2: 14::. Is::!,.

1 la. ZissermRn, L., anal liivh, I,. : Ihl~liplasis au11 Treatment of l’oison Ir;v Dermati’tis >Vitli an Estrwt of Rhus Toxicotlenclron. J. AI,I,Kl<(;r 10: 596, 1939.

I:‘. Shehire, B.: Contact Dermatitis From Weeds, .T . A. RI. A. 113: 1085, 1939. I?,. Racouehot, J. : Drrmatose I’rofrssionellc7. Plantw B Rothme. Aw11. (1. 1~x1.

pl~ofrss. 2: 140, 19:;9. 14. Stramlbwg, J., Bonneric, I’., Bostriim, G., :rntl Hellerstriim, H. : Ocrupationxl

lhwatcwrs an11 Their (‘ontrol, Arta tleln,xt.-vcnerEo1. 20: fil::, 1!)39. 1.7. Bering, F.: B~grif&hestimmung dn Hrrufsllautkrankheiten (Dwmatitis, Abnnt-

zunwtlerrrx~tose. Ekzern) . Dernrxt. T~chnschr. 108: 216. 19:X). 1 (i. Flan&, E.,

, I

ant1 I<xl~r;ru, H.: Jiemarqucs sur I’iXologid et la pathogenic tleF flcrmatoses yrofrssionnelles lxtst:es sur l’olw5wtion tic 1,000 ws 11e drrmitc~x 11es tx~raillfwrs, Arcall. rl. mul. profess. 2: 247, 19:X).

424 THE JOURNAL OF ALLERGY

17. Flantlin, C., Rabeau, H., and Ukrainozyk: LOW cas de tlerrnites (surtoul eczema) chrz tles travaillcurs; triage, tests cutan&. >1rch. tl. lual. profess. 2: 284, 1939.

18. Watrous, R. M.: Dermatitis From Intlustrial Contact 1Vith Nicotinic Awl, J. A. M. A. 112: 2132, 1939.

19. Ziindel. W.. and Jentsch. M. : Alleraic Phenomena in Baker’s Eczema and Their

26.

21.

22.

23.

24.

25.

eti.

27.

as. 29.

30.

31.

32. 33.

34.

35.

36.

37.

38.

39.

30.

41.

42.

43.

44.

45.

Meaning, Arch. f. De;,mnt. u. SypTr. 178: 469, 193!l. Rabeau, H., and Ukrainczyk: Dermatitides of Laundresses : Role of Chromiunr

and Chlorine (in France). Ann. dermat. et syph. 10: 656, 1939. Klauder, J. V., Gross, E. R., and Brown, II. : Prevention of Industrial I)erum

titix With Reference to Hand Creams, Soap ant1 the Harmful Role of Some Cleansing Agents, Arch. Dermat. & Syph. 41: Xl, 1940.

Klumpp, T. G.: The New Federal Footl, Drug, am1 Cosmetics Act, .J. A. M. A. 113: 22x1, 1949.

Hollander, L. : Contact Dermatitis Due to l’ontocaine ~lytlroc~lllori~lr, Arc.11. Dermat. & Syph. 40: 93, 1939.

Goodman, M. H. : Cutaneous Hypersensitivity to the Procaine Anesthetics. Cor- relation of H.ypersensitirity With (‘hemica Structure, ,J. Invest. Dermat. 2: 33, 1939.

Jordon, J. W.: Contact Dermatitis From Opium l)rriratirea, J. A. M. A. 113: 1955, 1939.

Lamb, J. II.: Quinine Dermatitis From Anacin, Arch. Dermat. & Syph. 40: 803, 1939.

Lerison. L.. and Harrison. J. J.: Dernmtitis Followina Theelin. J. A. nl. A. 113: ‘20&, 1939. ’

Madden. J. F.: Reactions in Tattoos. Arch. Dcrmat. & Svnh. 40: 2%. 1939. Bernstein, J. C. : Dermatitis Due to a’ Sulfur-Meat Compleii Report of a Case,

Arch. Dermat. & Syph. 40: 414, 1939. Be&et, P.: Patch Test : Evaluation of Possible Dangers, New York State .I.

Med. 39: 529, 1939. Rostenberg, A., Jr., and Sulzberger, M. 13.: Substances for Patch Testing an11

Concentrations to Be Used, J. Invest. Dermat. 2: 93, 1939. Guild, B. T.: BostrBm, G. :

Window Patch Test, Arch. Drrmat. & Syph. 39: 507, 1939. The Allergic Tissue Metabolism Reactron: A Correction, Acta

dermat:venereol. 19: 540. 1938. Sulzberger, M. B., I,oreman,’ A. B., Shelmire, Ii., Hecht, R., Rappaport, B. Z., ant1

Hoakins, J. G.: Svmposium on Allergic Dermatoses, J. QLLEFZY 11: 40. 19<, 1938-40. ” -

Tachau, P. : Problems of So-Calletl infantile Eczema: I. True Eczemq Acta dermat:venereol. 19: 58i, 1938.

Tachau, I~.: Problems of So-Calle~l infantile Eczema: II. Atopie Dermatitis, Acta dermat.-venereol. 20: 1, 1939.

Tachau, P. : Problems of So-Called Infantile Eczema : III. Reborrhoic Derma yip. $; soriasoids, YeborrhCids), General Survey, Acta dermat:venereal. 20:

<. . . Lippaid, V. W. : Immunologic Response to Ingestion of Foods by Normal and by

Eczematous Infants, Am. .J. Dis. Child. 57: 524, 1939. Anderson, A. F., Scldoss, 0. M., and Myers, F.: The Intestinal Absorption

of Incompletely Digested Protein by Normal Infants, Proc. Sot. Exprr. Biol. & Xled. 23: 180, 1925.

Simon, F. A., and Rackemann, F. M.: The Development of Hypersensitiveness in Man: I. Following the Intradermal Injection of the Antigen, J. AIJ,EI:GY .I - 5: 439, 1934.

Clein, N. W.: Allergy in Infants. The First Allergic Manifestations, J. ALLERGY 10: 253. 1939.

Feinberg; S. M.: Seasonal Atopic Dermatitis. The Role of Inhalant Allergens, Arch. Dermat. & Syph. 40: 200, 1939.

Laymon, C. W., and Gumming, H.: Histaminase in the Treatment of Urticnria and Atonic Dermatitis, J. Invest. Dermat. 2: 301, 1939.

Traut, E. i.: Management of Intractable Urticaria, Arch. Dermat. & Syph. 40: 365, 1939.

Markel, J. : Chronic Relapsing Urticaria and Angioneurotic Edema: Report of a Case With Associated Pancreatic Insufficiency and Relief by Oral

1 ‘Administration of Deinsulinized Pancreatic Extract, Arch. Dermat. & Syph. 39: 992, 1939.

426 THE JOURNAL OF ALLERGY

Gougerot, H. : Synth&e pathoghnique. ~ryth&me noueux. Dermatitis nodularis. Orytheme polymorphe. Syndrome allergique de causes differentes sur un m&me terrain allergique ou hyperallergique, Bull. Hoc. frana. de dermat. et syph. 45: 1195, 1938.

Xerklen. P.. Jacob. A.. Mayer. Oudet. and L&v. F.: Quelaues CBS d’Brvth$me noue;x chez 1 )adulte; Bull. 6oc. fra&. de de&&t. et syph.b;5: 1134, 1958.

Pautrier, L. M., Ullmo, A., and Baumeister. P.: L %&h&me noueux au cows de diverses &fection$ B&l. Sot. frang. de’ dermat. et -syph. 45: 1207, 1938.

Rabeau, H., and Ukramczyk : Tests biologiques dans 1’6ryth8me noueux de l’adolescence. Bull. Sot. franc. de dermat. et svuh. 45: 1125. 1938.

Ramel : Des indications fouriies par 1’6tude A Ctiopathog&ique de 36 (‘as d’&yth&me noueux, Bull. Sot. frany. de dermat. et syph. 45: 1138, 1938.

Stiihmer, A. : Contributions cliniques b 1’6tude de l’Bryth8me noueux, Bull. Sot. frang. de dermat. et syph. 45: 1240, 1938.

73. Wiesmann, E.: Zur Kasuistik der Trichophptide, Dermatologica 79: 291, 1939.