Historical Aspects of Blistering Eruptions EMILIANO PANCONESI, MD

I f the first professor of our specialty in the world was Vincenzio Chiarugi,’ the lirst author of a treatise, in the modern sense of the word, was Joseph von Plenck. “L’infaticabile Giuseppe Plenck,” as Chiar-

ugi called him, in 1766 attracted widespread attention when he proposed a cure using a mixture of mercury and gum arabic (mercurius gummosus Plenckiil in his book on venereal disease. Although this treatment may have pro- duced improvement in some syphilitics, it surely allowed its inventor to present the 6rst modern description of a side effect: the troublesome salivation caused by mer- c~ry.~ The future was to witness the arrival of a myriad of drugs for syphilis and other diseases, almost all with pos- sible unwanted side effects, including blistering cutane- ous eruptions. Then came the discovery of the queen of antiluetic drugs, penicillin, to which a witty authoP dedi- cated this clever adaptation of a children’s song:

Mother, mother, I am ill! Call the doctor from over the hill! In came the doctor, in came the nurse, In came the lady with the alligator purse. Penicillin, said the doctor Penicillin, said the nurse Penicillin, said the lady with the alligator purse.

Brief History of Blister Eruptions, Spontaneous and Drug Induced I do not have the space to cover the complete history of each affliction considered in this paper. I note, however, that problems of historic semantics make it difficult to compare the terms used in the past with those used today. In the endeavor to treat the principal blistering eruptions

From the Department of Dermatology I, University ofFlorence, Florence, Italy.

Address correspondence to Emiliano Panconesi, MD, Direttore Istituto di Clinica Dermatologica, Via Alfani, 37, 50121 Firenze, Italy.

together we must mention some references to our topic in protodermatology. The possibility of individualizing in the ancient descriptions the forms that correspond to the blistering eruptions as we know them begins with Aulus Cornelius Celsus. In the fifth book of his De medica libri octo, this great Roman doctor (25 - 30 B.C.E. to 45 - 50 ce), who probably acquired much of his knowledge from the Greeks Hippocrates and Asclepiades, distinguishes dif- ferent types of “papules” and describes the “superficial” ones as having a morphology very similar to that of “her- petit” or “vesicle-like” lesions. In his nomenclature we find the terms impetigo and formica (papular and vesicular elements), both closely related to our topic. Claudius Ga- lenus (Pergamum 131, Rome (?) 201), one of the most distinguished physicians of antiquity and author of some 400 books(!) wrote on herpes and phlyctenae, including cases of artifactitious origin.

In the Middle Ages the Hebrew term zaraath (trans- lated as “lepra, ” “leprosy”) actually corresponds to various eruptions, including eczema. Another ident& able reference to eczema, in particular to atopic dermati- tis, is found in Guglielmo Saliceto (1210- 1277), who wrote of “lactumen in capitis puerorum, “ indicating, per- haps for the very first time, a relationship between milk and this eczematous eruption in infants.

In the Renaissance, Gerolamo Fracastoro (1478 - 1546), better known for having baptized as syphilis this then newly arrived disease, in his De contagione et conta- giosis morbis . . ., indirectly referred to the ante-litteram infectious eruptions, including the blistering ones.’ I note, however, that actually blister eruptions are less cited in the ancient literature than are other elementary morpho- logic lesions.

To exemplify still another period we refer to France and the great Alibert’s famous treatise5 in which he arranged all (or almost all) the blistering eruptions in his First Order (“eczematous dermatoses”) and Third Order (the “tineas”) (Table 1).

0 1993 by Elsevier Science Publishing Co., Inc. l 0738-081x/93/$6.00 437

438 PANCONESI

Table 1. Possible Equivalents of Blister Eruptions in Aliberf’s Classification

First Order (eczematous dermatoses) Genus (II) of erysipelas

Species of edematous type with phlyctenae Genus (III) of pemphigus

Synonyms: pemphix, vesica, pompholyx (diutinus), morbus vesicularis, febris bullosa, morbus phlyctenoides (herpes phlyctenoides), erysipelas vesicolosum, blasscheu, blatterchen

Genus (IV) of zosfer Synonyms: ignis sacer of Pliny, herpes zoster (Willan), zona repens rignea (Hoffmann), shingles, @irter

Genus (V) of phlyzacion Synonym: ecthyma of Willan

Genus (VI) of cnidosis Synonyms: nettle rash, nesselauschlag, porcellana, essera (of the Arabs), urticaria (bulIous variety)

Genus (VII) of epinycfis Synonyms: essera noctuma (Avicenna), uritis noctuma (Plenck)

Genus (VIII) of olophlyctis Synonyms: herpes (miIiaris, labialis, praeputialis or progenitalis),

volatilica (of infants)

Genus (I) of ucor Third Order (tineas)

Synonyms: crusta lactea infantum (Plenck), lactumen, gourme, milk crust, milchschort, melk horst

Aetius of Amida (6th century CE), cited by Unna, wrote about “em eczemata ab ebullienfe fenme Grueci vu@ appeZlant.“Then some centuries later Robert Willan (1757- 1812) used this old phrase for those vesicular eruptions provoked by many external irritants (which were to be called “chemical,” including drugs, in the fu- ture). The contemporary Thomas Bateman, as well as Pierre Rayer, Alphonse Devergie, Ferdinand Hebra, John Laws Milton, Thomas M’Call Anderson (1836- 1908), Paul Gerson Unna (seborrhoeal eczema, 1887), Ernest Besnier, Louis Brocq, Jean Darier, and many others all had a part in establishing the scientific monument to ec- zema.2

Regarding pemphigus,“ this term appears to have been used for the lirst time by Francois de Sauvages (1760) who, as Linnaeus and Thomas Sydenham did for plants, arranged diseases in an “order - genus-species” nomen- clature. References had been made to pemphigoid fever, febris bullosa, long before. Bazin, Hebra, and Kaposi all treated these bullous dermatoses, but it was Duhring (1884) and Brocq (1880) who made the distinction be- tween pemphigus and pemphigoid. The histologic speci- fications (Civatte, 1936), cytodiagnostic test (Tzanck, 1946), individuation of pemphigus antibodies (Beutner and Jordon, 1964), and finally the discovery of penicillin- induced pemphigus (Caccialanza et al, 195 1; Ruocco et al, 1979) are all milestones in the modem history of this autoimmune affection.

Clinics in Dermatology 2993;11:437-439

I note Alibert’s report of a herpetic-type eruption in a man who used a strong topical drug to treat plantar hyper- hidrosis.5 Actually the real history of drug reaction begins about a century later with Heir&h Koebner, who in 1877 described a quinine-provoked eruption. Then, as Laugh- lin and Jackson remind us in their article,’ Prince A. Morrow reviewed “the etiology and pathogenesis of drug eruptions” in 1883. He described the irritant idio- syncratic effect of drugs on the skin, the physiologic (pathophysiologic) blebs of cantharides; other “blister” eruptions, like pemphigus, zoster, and eczema were to be considered neuropathic and thus also idiosyncratic drug eruptions.

In 1906 von Pirquet introduced the concept of allergy, the basis of an “allergic” interpretation of eczematous dermatoses and other chemically caused eruptions. The first patch test (with a primula leaf) was done by John Ferguson in 1890,* preceding the better known test that gave a positive local reaction to mercury.9 The “toxicolo- gic” manifestations of erythema multiforme,* pemphi- gus, and herpetic eruption can be referred to cutaneous allergy induced by arsenicals.1° Curtis and Crawford in 1951 obtained positive (eczematous) reactions to patch tests with para-aminobenzoate and other sensitizers”; in 1958 Epstein described the first case of contact dermatitis caused by the antibiotic neomycin.12 Finally, I note the 1938 report of a case of Stevens- Johnson syndrome pro- voked by diphenylhydantoin.*3 At this point in time, however, the reports become too frequent and are no longer history.

References 1.

2.

3.

4.

5.

6.

Marri Malacrida L, Panconesi E, Holubar K. Vincenzio Chiarugi (1759 - 1820): The academic career of the first professor of skin diseases. Ital Gen Rev Dermatol 1991;28:129-40. Crissey JT, Parish LC. The dermatology and syphilology of the nineteenth century. New York: Praeger, 1981:16-7, 332-51. Whorton J. “Antibiotic abandon”: The resurgence of thera- peutic rationalism in the history of antibiotics. In: Parascan- dola J, editor. A symposium. Madison: American Institute of History of Pharmacy, 1980: 125-36. Fracastorii H. De contagione et contagiosis morbis et eorum curatione. Venice, 1546. Alibert GL. Trattato compiuto delle malattie della pelle. Venice: Antonelli, 1835 (Italian translation by MG Levi). Fabbri P. Pemfigo. In: Serri F, editor. Trattato italiano di dermatologia. Padua: Piccin, 1984;66:1-2.

*For the history of erythema multiforme, see the article by Fubbri and Punconesi in this issue.

Clinics in Dermatology 1993;11:437-439

7. Laughlin S, Jackson R. A brief history of drug reactions. Clin Dermatol 1986;4:1- 15.

8. Ferguson J. The primula obconica. Br Med J 1890;2: 954-5.

9. Jadassohn J. Dermatoses produced by drugs. London: New Syndenham Society, 1900: 170 (translated by Elkind).

10. Stokes JH, Beerman H, Ingraham NR. Modem clinical sy- philology. Philadelphia: WB Saunders, 1944: 241.

PANCONESI 439 HISTORICAL ASPECTS OF BLISTERING ERUPTIONS

11. Curtis GH, Crawford PF. Cutaneous sensitivity to mono- glycerol paraminobenzoic acid. Cleve Clin Q 1951;18: 35-41.

12. Epstein S. Dermal contact dermatitis from neomycin. Ann Allergy 1958;16:268-80.

13. Sparburg M. Diagnostically confusing complication of diphenylhydantoin therapy. Ann Intern Med 1963;56: 914-30.