Von Hebra Research Articles

Vitiligo in the 19<sup>th</sup>-century dermatological works of Vincenzo Chiarugi, Robert Willan, Jean-Louis Alibert, and Ferdinand von Hebra

Vitiligo is an iconic dermatological pathology as its clinical manifestations indelibly mark the patient through the appearance of white spots all over the body. The oldest written testimonies referring to vitiligo are: the first texts of Ayurveda, the Ebers Papyrus and the Leviticus of the Old Testament. During the Roman Empire, the doctors Aulus Cornelius Celsus and Galen, respectively in the I and II centuries AD, were the first to describe this skin disease and their statements were used by all subsequent authors. Hieronymus Mercurialis in the XVI century, Joseph Jakob Ritter Plenck in the XVIII century and Vincenzo Chiarugi again in the XIX century based their writings on the references of the two Roman doctors. After centuries of scientific inaction in the XIX century, there was an exponential increase in dermatological studies and the medical-scientific works produced in this period laid the foundations of modern dermatology. The nineteenth-century texts of Robert Willan and Thomas Bateman, Jean-Louis Alibert, Ferdinand von Hebra, and Moriz Kaposi proved fundamental for the study of skin pathologies, including vitiligo. The nineteenth-century medical-scientific vision and approach to vitiligo is shown in this work through the presentation of direct quotes extrapolated from the most important works of the authors mentioned above, this served to historically contextualize the gradual progress of medical study regarding this skin pathology.

H13 Leprosy and psoriasis: a heated controversy

Abstract In the Old Testament, the term ‘Lepra’ was used to describe many skin diseases, including psoriasis, eczema, vitiligo, alopecia areata and boils. The word ‘leprosy’ was derived from this and was previously used as a generic term that included multiple inflammatory dermatological diseases. It was a disorder of great religious significance during ancient times, with intense stigmatization—‘lepers’ were pronounced unclean by priests. Hippocrates (460–377 Bc), the Greek ‘father of medicine’, can be credited with being the first to separate medicine from religious superstition. However, there was little differentiation between leprosy and psoriasis, two distinct diseases we know today. He used the word ‘psora’ to describe itch, and ‘lopoi’ to describe the dry and scaly features of skin conditions, thus continuing the confusion between leprosy and psoriasis. The failure to differentiate psoriasis as its own clinical entity from leprosy meant that for many centuries, patients with psoriasis also suffered the same cruel fate as those with leprosy in society. Those suffering from leprosy were wrongly believed to be highly contagious and were forced to carry a bell or clapper to announce their approach to those who were considered healthy. They were required to wear distinctive clothing so that they were easy to recognize by the public, and were not permitted to talk to or even touch a healthy person. They were outcast in society and could only mix with other ‘lepers’. In 1313, Philip the Fair of France horrifically ordered all those outcasts to be burned at the stake. In 1809, Robert Willan (1757–1812), an English doctor, marvellously developed a simple classification of skin diseases that offered a clear description of the different types of psoriasis. This was a crucial milestone in the recognition of psoriasis as a separate skin disease from leprosy. However, while he was the first person to describe psoriasis as a separate condition, he failed to eliminate leprosy completely as an associated disease. He used the term ‘lepra vulgaris’ to discuss modern psoriasis, which once again further perpetuated the confusion between psoriasis and leprosy. Ultimately, it was Ferdinand von Hebra (1816–1880), an Austrian physician, who permanently shed the term ‘lepra’ from the description of psoriasis in the 1800s, finally allowing the two diseases to be separate.

Erythroderma (exfoliative dermatitis). Part 1: underlying causes, clinical presentation and pathogenesis.

Erythroderma (exfoliative dermatitis), first described by Von Hebra in 1868, manifests as a cutaneous inflammatory state, with associated skin barrier and metabolic dysfunctions. The annual incidence of erythroderma is estimated to be 1-2 per 100000 population in Europe with a male preponderance. Erythroderma may present at birth, or may develop acutely or insidiously (due to progression of an underlying primary pathology, including malignancy). Although there is a broad range of diseases that associate with erythroderma, the vast majority of cases result from pre-existing and chronic dermatoses. In the first part of this two-part concise review, we explore the underlying causes, clinical presentation, pathogenesis and investigation of erythroderma, and suggest potential treatment targets for erythroderma with unknown causes.

The rise of Chemical Peeling in 19th-century European Dermatology: emergence of agents, formulations and treatments.

Considering the increasing number of chemical peeling applications, also the interest in the history of chemical peelings and agents, has grown in dermatology. Research ascribes the first use of phenol as a chemical peeling agent to William Tilbury Fox (1836-1879) in 1871. Furthermore, Ferdinand von Hebra (1847-1902) is said to describe the properties of various peeling agents in 1874, and Paul Gerson Unna (1850-1929) adds resorcinol and trichloroacetic acid in 1882. To identify the first mentions of chemical peeling applications and agents in 19th-century dermatology. Nineteenth-century dermatologists were identified by an examination of literature of the last 30years on the history of chemical peeling. Systematic examination of the medical textbooks of Hebra, Fox and Unna was conducted. It was proved whether the mentioned agents were used for chemical peeling applications. The skin peeling property of phenol was already discovered by its first describer, the chemist Friedlieb Ferdinand Runge (1795-1867) in 1834. The Viennese dermatologist Hebra described phenol as a chemical peeling agent in 1860. Hebra and his associate Moriz Kaposi (1837-1902) stated that 'Lotio carbolica' was already used in London. Fox used phenol mostly as a disinfectant and not for chemical peelings since 1869. Unna described the chemical peeling property of salicylic acid in 1882 and gave the most comprehensive account of chemical peels of the 19th century in 1899. Unna also introduced the Gutta-percha plaster with salicylic acid and phenol. Around 1900, Unna was famous for his peeling paste with resorcinol in Germany. A new chronology of the introduction of chemical peeling in dermatology can be drawn from the results. The German-speaking dermatology pioneered the treatment of skin diseases with chemical peelings as well as for aesthetical purposes 21years earlier than hitherto known.

Eaux thermales et thermalisme en dermatologie au xixe siècle

Jean-Louis Alibert (1768-1837), Pierre-Alphée Cazenave (1802-1877) and Ferdinand von Hebra (1846-1880) are among the most famous names of the XIXth century dermatology. All were interested in hydrotherapy and mineral waters. Alibert was especially fond of sulfurous waters from the Pyrenees, for treating almost every inflammatory disease, like psoriasis, chronic eczema and even hair diseases or cheloids. He mentioned very often the use of mineral waters in his two masterpieces, Description des Maladies de la peau (1806) and Clinique de l'Hôpital Saint-Louis (1833). In case patients were not able to travel and spend times at thermal stations, he recommended artificial waters made by pharmacists in specialized places in Paris, consisting in water plus minerals, in order to obtain a composition close to natural spring waters. Around 1850, Cazenave also used mineral waters and hydrotherapy, mainly sulfurous waters. In Vienna, von Hebra was more reluctant to the use of mineral water, as he believed that the time spent in baths was more important than the composition of the water itself. Adrien Doyon (1827-1907), who translated Hebra's book in French, strongly disagreed with him, as he had a dermatology private practice in Uriage, in the French Alps. Modern hydrotherapy in dermatology is clearly in relation with this XIXth century tradition. © 2020 Elsevier Masson SAS. All rights reserved.

Stevens-Johnson Syndrome

Stevens-Johnson syndrome (SJS) is an immune complex mediated hypersensitivity complex that typically involves the skin and mucous membranes. While minor presentations may occur, significant involvement of oral, nasal, eye, vaginal, urethral, gastrointestinal, and lower respiratory mucous membranes may develop in the course of the illness. GI and respiratory involvement may progress to necrosis. Stevens-Johnson syndrome is a serious systemic disorder with the potential for severe morbidity and even death. The syndrome was first described in 1922, when the American pediatricians Albert Mason Stevens and Frank Chambliss Johnson reported the cases of 2 boys aged 7 and 8 years with "an extraordinary, generalized eruption with continued fever, inflamed buccal mucosa, and severe purulent conjunctivitis". Both cases had been misdiagnosed by primary care physicians as hemorrhagic measles. Erythema multiforme (EM), originally described by Von Hebra in 1866, was part of the differential diagnosis in both cases but was excluded because of the 'character of skin lesions, the lack of subjective symptoms, the prolonged high fever, and the terminal heavy crusting". Despite the presence of leucopenia in both cases, Stevens and Johnson in their initial report suspected an infectious disease of unknown etiology as the cause. In 1950, Thomas divided EM into 2 catagories: erythema multiforme minor (Von Hebra) and Erythema multiforme major (EMM). Since 1983, erythema multiforme major and Stevens-Johnson syndrome had been considered synonymous. In the 1990s, however, Bastuji and Roujeau each proposed that Erythema multiforme major and Stevens-Johnson syndrome are 2 distinct disorders. Several investigators propose that Stevens-Johnson syndrome and Toxic epidermal necrolysis (TEN) represent the same disease at different levels of severity. Although several classification schemes have been reported, the simplest breaks the disease down as follows: * Stevens-Johnson syndrome-A "minor form of TEN", with less than 10% body surface area (BSA) detachment. * Overlapping Stevens-Johnson syndrome/Toxic epidermal necrolysis (SJS/TEN)-Detachment of 10-30% BSA. * Toxic epidermal necrolysis-Detachment of more than 30%BSA.KYAMC Journal Vol. 8, No.-2, Jan 2018, Page 31-35

Herpes Labialis-Induced Erythema Multiforme along Blaschko's Lines.

Dear Editor: Erythema multiforme (EM), first described by Von Hebra in 1862, is an acute, self-limiting mucocutaneous condition induced by some immune reaction to infections or pharmacologic antigens1. The distribution of EM along Blaschko's lines (BL) is extremely unusual. A 28-year-old, non-consanguineous Hindu male patient presented with an asymptomatic linear lesion of 3 days' duration along with multiple vesicular eruptions over the right side of his upper lip for 5 days. The lesion consisted of multiple erythematous annular eruptions. He had a history of recurrent vesicular eruptions on the lip during the last 5 years. There was no other systemic illness or history of similar skin rash. Physical examination revealed the presence of multiple, discrete, small target-like lesions, most having a central dark spot, on the right forearm along BL. Some lesions were confluent, forming a bigger and irregularly shaped lesion. A group of tiny vesicular eruptions were present on the upper lip (Fig. 1A, B). Fig. 1 Erythema multiforme on the right forearm along Blaschko's line. Insets: (A) grouped vesicles with crusting due to herpes labialis on the upper lip, (B) close-up of the target lesions. (C) Low-power view (H&E, ×100) showing an intact epidermis ... It was diagnosed clinically as EM along BL with recurrent herpes labialis. Routine tests of blood, urine, and stool samples showed no abnormality. Biopsy and histopathological examination from a lesion on forearm revealed exocytosis, extensive interface dermatitis, necrotic keratinocytes, dermal edema, and mononuclear cell infiltration in the upper dermis (Fig. 1C). Proposed mechanisms of EM include type IV hypersensitivity immune response mediated by T lymphocytes2, genetics and infections. The most possible etiologic factor is herpes simplex virus. Infection due to Mycoplasma pneumoniae, vulvovaginal candidiasis, hepatitis C virus; drugs like acetaminophen, penicillin, and sulfonamides; and diseases like systemic lupus erythematosus (SLE), small vessel vasculitis, urticaria, and granuloma annulare are also implicated. The lesions of EM usually start in a symmetric fashion over the acral areas and extensor surfaces of the limbs, and progress centripetally. Koebnerization may influence the distribution. BL are known to represent mosaicism3. Besides nevi, autosomal and X-linked dominant diseases; polygenic diseases such as lichen planus, psoriasis, eczema, SLE, pemphigus vulgaris, granuloma annulare, linear drug eruption, and graft-versus-host disease may also be distributed along BL. In polygenic diseases, distribution along BL as an isolated manifestation or as a superimposed manifestation on classic generalized disease may occur owing to postzygotic mutation involving one of the predisposing genes. This is also known as loss of heterozygosity (LOH), which gives rise to a patch of homozygous or hemizygous tissue. The possible mechanisms for the development of LOH are mitotic recombination, gene conversion, point mutation, deletion, or mitotic nondisjunction. Blaschko-linear EM is extremely rare and has been described in only two cases (Table 1)4,5. None of these previous cases involved active herpes labialis at the time of presentation. One of them, however, involved a history of recurrent herpes labialis5. The case reported by Micalizzi and Farris5 was linear; however, morphological assessment of the lesions was difficult with the clinical photograph provided. Our case possibly is the first case of EM associated with active herpes labialis and with a distribution along BL. This case provides strong evidence in support of a genetic mechanism in the pathogenesis of EM. Table 1 Comparing all published cases of linear erythema multiforme4,5

Teaching and Learning in Dermatology: From Gutenberg to Zuckerberg via Way of Von Hebra

The World Wide Web (www) and other internet-based technologies offer enormous potential for enhancing teaching in dermatology. There is also the possibility that if these technologies are adopted uncritically, either because of ignorance of how people learn, or because they are viewed primarily as ways to reduce institutional costs, that they might diminish learning, thereby reducing the value proposition that undergraduate students receive from Medical Schools. I review the history of recent technological change with a focus on what value such technologies bring to both student and institution. After summarising some of the core principles underpinning successful learning, and modern theories of medical expertise, I critically discuss some of the ways the Web and allied technologies might enhance the learning of dermatology.

History of German language dermatology

History of German language dermatology

Shape and configuration of skin lesions: Targetoid lesions

What is probably the first description of targetoid or iris lesions, as they appear in erythema multiforme (EM), can be found in Thomas Bateman's 1836 textbook “Practical Synopsis of Cutaneous Diseases According to the Arrangement of Dr. Willan.” EM was initially described by Bateman and later by von Hebra as an acute self-limiting skin disease, symmetrically distributed on the extremities with typical concentric “targetoid” or “iris” lesions, and often recurrent. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) were added to this syndrome later. A newer classification has created two disease spectra: EM consisting of EM minor and EM major (or bullous EM), and SJS and TEN. EM minor and EM major are often recurrent, postinfectious (especially after herpes and mycoplasma) disorders with low morbidity and almost no mortality. SJS and TEN are usually severe drug-induced reactions with high morbidity and poor prognosis. The target lesions found in each form of the disease are described and defined. Although the term “target lesion” originated from the description of EM and despite its being the dominant lesion in this disease, it is not pathognomonic for EM, and these lesions can sometimes appear in other diseases. Short descriptions of these other diseases are presented.

Excimer laser: a treatment option for the prurigo form of atopic dermatitis

The term prurigo, originating from pruire (itching), was coined by Ferdinand von Hebra in 1850, characterizing typical itching papules and nodules induced by scratching [1]. Since then, various epo...

The continuing rise of contact dermatitis, Part 1: The academic discipline

This article describes the history and development of contact dermatitis as an academic discipline, from early observations documented in ancient Egypt and Greece, to the current medical specialization we know today. Given its essential role in clinical diagnosis, the history of patch testing is also discussed, including the pioneering work of Städeler, von Hebra, Jadassohn, and others. The historical development of some international societies for contact dermatitis is provided, along with some discussion on bibliometric performance in this field. Overall, it can be seen that from humble beginnings, contact dermatitis is now thriving as a specialized field in clinical dermatology.

Rhinoscleroma: case report

Rhinoscleroma is a chronic granulomatous, slowly progressive infection that affects the nose and other respiratory tract structures. It was first described in 1870 by dermatologist Ferdinando Von Hebra and posteriorly named respiratory scleroma, which emphasizes involvement of upper and lower airways [1]. It occurs frequently in the nasal fossae, eventually extending itself to the larynx, the rhinopharynx, the mouth and the paranasal sinuses; the lips, trachea, and bronchi may also be affected to a lesser degree. Extrarespiratory involvement has rarely been described. Scleroma is endemic in some Central American countries, Indonesia, India, Poland, Hungary, Russia, and some African countries. In China the frequency of this disease is low. The regions of endemicity is Shandong province. The infection is due to a capsulate gram-negative bacterium, Klebsiella rhinoscleromatis, which was first described by Von Frisch in 1882 [2].

Dermatologists Honored on Stamps

Eight dermatologists have been honored with their pictures on stamps: Ferdinand Ritter von Hebra, Jean Alfred Fournier, Moritz Kaposi, Armauer Hansen, Niels Finsen, Hulusi Behcet, Franz Hemerijckx, and Ruzar Briffa. Of these, Finsen also received the Nobel Prize-one of the highest honors for a physician or scientist. He was awarded the 1903 Nobel Prize for Physiology or Medicine recognition for his contributions to the treatment of diseases-especially lupus vulgaris-with concentrated light radiation, whereby he opened up a new avenue for medical science. 1(P322) Finsen was the first to appreciate that UV light had a curative effect on skin diseases, and he also discovered that the suppuration in smallpox can be prevented by screening the patient from UV rays. One of the dermatologists, Briffa, was honored not as a dermatologist but as a well-known poet and national literary figure of Malta.

Adolf Jarisch (1850–1902): an important contributor to Austrian dermatology

Adolf Jarisch was born on the 15th of February 1850 in the city of Vienna, where he also studied medicine. He soon pursued a career in dermatology and venereology and, thus, joined the clinic of von Hebra, one of the founders of the famous new Vienna School of Medicine. After temporarily replacing von Hebra, Jarisch became the chief of the Department of Dermatology at the University of Innsbruck (1887). Although Adolf Jarisch was appointed chief of the dermatologic department at the University of Graz 5 years later (1892), his biggest dream, to become successor of his former teacher Ferdinand von Hebra and head the dermatological department of the Wiener Allgemeines Krankenhaus (Vienna General Hospital) did not come true. Although Adolf Jarisch is mainly known for his observations on skin reactions and a profound worsening of symptoms in syphilitic patients immediately following treatment with mercury (Jarisch-Herxheimer reaction), he authored more than 25 scientific articles and wrote a book, "Hautkrankheiten", which was considered as the most important in German-speaking literature at the beginning of the twentieth century. The purpose of this historical article is to discuss Jarisch's achievements in the field of dermatology based on a detailed analysis of his scientific work.

Carl Egyd Ritter v. Rzehaczek (1816-1897): painter, sculptor and surgeon.

Carl von Rzehaczek was a classmate and contemporary of Ferdinand von Hebra, who founded the tradition of painter-physicians at the Vienna School of Dermatology. The following reminiscence shall bring him to the attention of the reader.

Papillary tip bleeding or the Auspitz phenomenon: A hero wrongly credited and a misnomer resolved

H istoric investigation can unearth facts that invalidate details of teaching in medical schools and residency programs. The socalled Auspitz phenomenon is a good example; it is a misnomer. Heinrich Auspitz (1835-1886) was the early star among Ferdinand Ritter von Hebra’s pupils. Two years older than Moritz Kaposi (Kohn), dealing with histopathology and systematization earlier on, and editor (with Filipp Josef Pick) of the Archiv fur Dermatologie und Syphilis in 1869, he dropped out of Vienna University only in 1872 when he founded the Wiener Allgemeine Poliklinik and put himself in juxtaposition with Hebra (and Kaposi). Some time ago, while still in Jerusalem (K.H.), the centenary of his demise was addressed.1 Thoughts relating to this clinical sign, eponymously termed “Auspitz,” surfaced then but remained unpublished and have not been pursued until now. Major current texts such as Fitzpatrick’s DIGM2; the volumes by Rook et al (Champion et al3); Ackerman’s dermatopathology text4; Leider and Rosenblum’s dictionary,5 including Carter’s edition of 19926; and recent reports7,8 associate the papillary tip bleeding that occurs after scratching off the scales of a psoriatic papule with Auspitz’s name. However, the French Dermatologie et Venereologie of Saurat et al9 and, most remarkably, the (Austrian-only) volume by Fuhs and Kumer10 do not. Teachings in medical school and during residency in Vienna, Austria, where Auspitz lived, worked, and died do not mention any Auspitz phenomenon. “Why?” one might ask. Auspitz and Kaposi, two of the many Jewish assistants Hebra had in his fold, obviously were not the best of friends but, rather, emotional competitors. Kaposi,11 in the hailed, second French translation of his textbook, mentions the capillary tip bleeding but makes no relation to Auspitz. In a footnote by the translators Adrien Doyon and Ernest Besnier, the fact is addressed that both Devergie jeune and Hebra (eg, in 186012 and 184513) had observed this clinical sign earlier. We could not find evidence of this in Devergie’s textbook, but had no access to his extended bibliography. Going back in time, one may find that, surprisingly, Robert Willan14 already addressed this fact while writing on psoriasis (“. . .should any portion of the diseased surface be forcibly excoriated, there issues out a thin lymph, mixed with some drops of blood*. . .”). Even more interestingly, the asterisk points to a reference of Joseph Plenck15 in Vienna, Austria, which reads: “. . .squamae. . .quae tam digitis aufferi possunt, quam per sudores decidunt, quibus demptis profluit sanguis.” Going further back in time, one arrives at Daniel Turner’s treatise16 (“. . .as to the Strata above-mentioned, I had lately an Opportunity of remarking them, in an Elephantiatical Patient, on the Inside of whose Knee a large Lichen, or impetiginous Eruption, was seated, accompanied with great itching: Whence, upon rubbing, a Scale should throw off, and a fresh one regenerate in few Days. For curiosity sake, I raised one of these, near the Compass of an half Crown; in one Part it adhered to that subjacent, and forcing the same off with the Edge of my Spathula, several small Specks of Blood appeared underneath;. . .”). At this point in time and in historical investigation an additional difficulty emerged, which, so far, has not been overcome. Before Willan (the first printing of the first order of his textbook was in 1798), there is no dermatology in the modern sense. Sifting From the Institute for the History of Medicine at University of Vienna and Croatian Academy of Sciences and Arts, Zagreb. Funding sources: None. Conflict of interest: None identified. Reprint requests: Karl Holubar, MD, FRCP, Institute for the History of Medicine, University of Vienna, Wahringer Str 25, A-1090 Vienna, Austria. E-mail: KH.histmed@univie.ac.at. J Am Acad Dermatol 2003;48:263-4. Copyright © 2003 by the American Academy of Dermatology, Inc. 0190-9622/2003/$30.00 0 doi:10.1067/mjd.2003.89

From the New World. Louis A. Duhring and dermatitis herpetiformis

Louis Adolphus Duhring (born December 23, 1845) died in Philadelphia, the city of his birth and life work, on May 8, 1913. After medical school, he studied for two years in dermatology departments in London, Paris and Vienna. As a student in Vienna, he was under the tutelage of Ferdinand von Hebra, when the brilliant clinician and teacher was at the zenith of his fame. Duhring's series of 18 papers--published between 1884 and 1891--gave him an important and recognized position as one of the leading dermatological thinkers of the world. These publications described the skin disease which he named "dermatitis herpetiformis" (Duhring's disease). His assertion that dermatitis herpetiformis was a distinct dermatological disease process aroused at first considerable opposition. Moriz Kaposi, at that time the doyen of the Vienna school of dermatology, attacked his views with vigor and tenacity. Louis A. Duhring--this modest, unassuming, quiet-working, gentlemanly physician--made monumental contributions to American dermatology and played a significant role in establishing Philadelphia as one of the great centers of dermatologic activity.

Bupropion-Induced Erythema Multiforme

Bupropion-Induced Erythema Multiforme

ECZEMA AND FOOD HYPERSENSITIVITY

Prior to Columbus' voyage to the New World, an Italian physician, Paolo Bagellardo, wrote the first known scientific discussion of eczema in a pediatric textbook, Libellus de Aegretudinibus Infantium. The chapter on skin outlined recommendations for lubricating the skin and preventing scratching in children with this skin disorder. In the early 1600s, Helmont noted the association between a pruritic skin rash and asthma, and about 250 years later von Hebra described the flexural distribution of a chronic itchy skin disease. 34 However, it was the French physician, Besnier, who provided the first comprehensive description of atopic dermatitis in the late 1800s. 6 He emphasized the hereditary nature of the disorder, its chronic course, and its association with hay fever and asthma. Wise and Sulzberger 92 coined the term atopic dermatitis, further emphasizing the relationship between atopic eczema, asthma, and hayfever. The incidence of atopic dermatitis has been increasing over the past 40 years and now is estimated to affect between 12% and 15% of the pediatric population. 35 Atopic dermatitis [AD] is one form of eczema, which generally begins in early infancy and is characterized by extreme pruritus, chronically relapsing course, and distinctive distribution. AD is typically the first manifestation of a child prone to develop atopic disease, with 50% of all AD developing in the first year of life and 80% by 5 years of age. Approximately 80% of children with AD develop asthma or allergic rhinitis, with many losing their AD with the onset of respiratory allergy. The acute rash of AD is typically an erythematous, papulovesicular eruption, frequently with weeping and crusting that is more commonly seen in early life. It typically progresses to a subacute form marked by erythema and scaling papules, and especially in older patients, to a chronic form characterized by thickened, lichenified skin and fibrous papules. 9 The distribution of the rash varies with age, 38 involving the cheeks and extensor surfaces of the arms and legs in infancy, the flexor surfaces in the young child, and flexor surfaces, hands, and feet in the teenage patient and young adult. AD is identified by a constellation of symptoms. The diagnostic criteria proposed by Hanifin and Rajka 36 are an accepted standard for diagnosing AD, and the SCORAD Index, 24 adapted by the European Task Force on Atopic Dermatitis provides a standardized method for gauging severity. The pathogenic role of allergy in AD has been debated since Besnier's original description; however, recent studies delineating the immunopathogenic role of IgE-bearing antigen-presenting cells [APCs; e.g., Langerhans' cells and other dendritic cells] in establishing the Th2 lymphocytic response and of the IgE-mediated late-phase response in provoking cutaneous inflammation are compelling. Acute skin lesions of AD are described as spongiotic, with epidermal hyperplasia and ballooning of the keratinocytes secondary to intracellular edema. Mast cell and basophil numbers are normal, and eosinophils are rare. 83 In chronic skin lesions, the epidermis has moderate to marked hyperplasia, with elongation of the rete ridges and prominent hyperkeratosis. Spongiosis is variable and the number of mast cells and Langerhans' cells are significantly increased. Eosinophils are sparse. Demyelination and fibrosis of cutaneous nerves are observed at all levels of the dermis, and capillary numbers are often increased.