From the historic perspective, atopic dermatitis has gone through several evolutionary periods of understanding and development.
From ancient times to the 18th century, medical communities started to recognize a type of itchy skin disease. Although the term eczema had been used, no unified concept had been developed and no understanding of its underlying pathophysiology was established.
The 19th century witnessed the rapid development of dermatology as a specialty, with the effort of classifying skin diseases based on clinical findings, and the recognition of acute and chronic forms of eczema, the infant onset of eczema, and the systemic link between atopy of skin and atopy of the respiratory system.
By the 20th century, the dermatology community formed a unified concept of atopic dermatitis from divergent hypotheses under the framework of the cutting-edge science of the immune system to explain the pathophysiology of disease, leading to the coining of the term atopic dermatitis to establish a set of diagnostic criteria and a link between skin atopy and allergic mechanisms.
From the historic perspective, the approach of managing eczema has gone through multiple modifications as disease pathophysiology became more well delineated.
To introduce the subject of historic perspective on eczema, the following quote serves nicely:
Eczema has been rightly called the keystone of dermatology, and he who fully masters its management is not only skilled in regard to treating one of the most common and distressing of all cutaneous diseases, but has acquired a knowledge of the principles of dermatologic practice which will assist in the treatment of many, if not all, other maladies of the skin. l. duncan bulkley ( Eczema and its management: A practical treatise based on the study of three thousand cases of the disease , 1881)
As early as 1881, the medical community recognized the importance of eczema as a skin disease of high impact in medicine and in society. In this chapter we discuss the history of eczema from the perspectives of three historical time frames: ancient times through the 18th century, the 19th century, and the 20th century. We then discuss the historical approach to eczema treatment.
Ancient history and middle ages, through the 18th century
Eczema has presumably afflicted humans since well before the advent of written language. Healers and historians of antiquity have documented pruritic rashes and their remedies with great accuracy and astonishing classification systems. Unfortunately, interpretation of these ancient writings is often difficult and contentious at times. Though the first accepted report of a medical condition resembling atopic dermatitis (AD) is commonly cited as Suetonius’ account in The Twelve Caesars , it is important to note the centuries of pre-Roman medical accounts of pruritic dermatoses that afflicted these early civilizations and examine the practices surrounding the treatment of these conditions ( ).
The Ebers Papyrus, a compilation of hieratic writings dating to 1500 B.C.E., describes accounts of many skin ailments and popular Egyptian remedies of the time. Several portions of the 65-foot-long scroll depict eczema affecting the scalp, which likely were manifestations of seborrheic dermatitis ( ). Many topical remedies for cutaneous conditions were described in these writings, including modalities such as emollients, physical abrasives, lactic acid, the first descriptions of phototherapy with coingestion of the weed Ammi majus , and “heliotherapy” applied to the lesion ( ). A shard of Egyptian pottery from the Toronto Museum depicts a case of copper-induced contact dermatitis, with a secondary infection of weeping eczema productive of an odor resembling rotten fish eggs ( ). While the ancient Egyptians described numerous different cutaneous conditions, no specific reference to AD or eczema as a distinct entity has been identified.
Across the Red Sea, the civilizations of Mesopotamia also documented many dermatologic lesions in cuneiform tablets from the first millennium B.C.E. Unfortunately, the inhabitants of ancient Mesopotamia failed to preserve their deceased as well as their Egyptian counterparts did, thus precluding any correlative approach to understanding Akkadian words representing ailments of the skin. This has created contention among Akkadian scholars over the correct translations of medical terms. argues that the moist lower extremity skin lesion known as “rułibłu” describes a weeping eczema found in both children and adults. note in their review of writings from Ashur, Babylon, and Nineveh that the quantity of descriptors used to classify skin lesions in Mesopotamian works far dwarfs those of any other organ system of the body, thus reflecting an ancient appreciation for the diverse ailments of the skin. “KURAšTU” is commonly translated as eczema by cuneiformists, though Scurlock and Andersen more recently favor a translation of ringworm based on descriptions of clinical features. Given the difficulty of ensuring accurate understandings of Mesopotamian descriptions of these skin lesions it is not surprising that few texts on the history of AD have confidently included these pre-Roman accounts in their historical canon of ancient dermatologic literature.
Roman historian Suetonius described the first entity truly matching our modern concept of AD in his annals of the Julio-Claudian dynasty. Several family members, including Emperors Augustus and Claudius, were afflicted with a syndrome that appears to have features of the atopic triad ( ). Notably, Augustus suffered from bouts of asthma, rhinitis, and eczema; Claudius developed a horse dander allergy and recurrent attacks of rhinoconjunctivitis. In 543 C.E. the Byzantine physician Aëtius of Amila used the term eczema to describe “hot and painful phlyctenae which do not ulcerate” ( ) and was credited with being the first to associate the word with descriptions of “eruptions consisting of small pustules, accompanied by burning sensation and pain, which sometimes spread to the whole body” ( ).
Medicine during the second millennium C.E. in Europe owed much to the works of Persian physician and scholar Abu ‘Ali al-Husayn Ibn Sina, known as Avicenna. His encyclopedia, The Canon of Medicine , was translated into Latin in the 12th century and became standard reading for medieval era medical students in Europe and the Islamic world until the 17th century ( ). Sir William Osler considered this text “a medical bible for a longer time than any other work” ( ). Mentions of eczema are found in his sections on swellings, of which there are watery, gaseous, and papular subtypes. He classifies “certain forms of eczema” as papular inflammatory swellings. Inflammatory swellings are due to a “corporeal change showing that material has been removed from one tissue to another” known as a “catarrh” ( ). This latter term would appear many times in the literature through the 19th century.
Eczema as a term originated from the Greek word meaning “to bubble, to boil over, or to burst,” and it was used by Hippocrates in his writings on disorders of the skin (460–377 B.C.E.), including the Corpus Hippocraticum ( ). Hippocrates had a remarkably advanced understanding of physical exam findings as external manifestations of systemic diseases, including recognition of finger clubbing as a sign of occult lung cancer ( ). One of his well-cited accounts of an Athenian man “taken by itching over his whole body, but especially on his testicles and forehead” who then developed “lepra (white scale) to the view” and passed away is referred to by some dermatologic historians as a possible instance of AD. Others, however, contend that this case report is more consistent with a presentation of scabies in light of his prescribed regimen of a sulfur bath and subsequent development of “dropsy” or generalized edema and a rapid-onset fulminant outbreak ( ).
Italian physician Girolamo Mercuriale (1530–1606 C.E.) published the first modern book on dermatologic conditions, De Morbis Cutaneis , which featured accounts of infantile pruritic disorders of the head and neck resembling infantile eczema ( ). In 1763, François Boissier de Sauvages de Lacroix (1706–1767) coined the term tinea lactea to describe this skin condition of newborns, and Jean-Louis Alibert further described teigne muqueuse, achor muqueuse as precursors to the modern clinical entities of AD and seborrheic dermatitis ( ). These early French dermatologists adopted an understanding of skin disease in line with Hippocrates’ humoral theory in which patients would sometimes be advised that no treatment was necessary because rapidly altering a patient’s equilibrium state could do more harm than good.
The 19th century
The 19th century was a time of rapid development in dermatology. In 1801, the opening of the Hôpital Saint-Louis gave way to a wave of influential French dermatologists, including Ernest Henri Besnier who would become the medical director. Besnier coined the term prurigo diathésique ( ). A major innovation in the field was the development of a schema for classifying lesions by Robert Willan and Thomas Bateman. Prior to the 19th century, F. B. de Sauvages of Lyon created a simple system of symptom-based features ( ). Antoine Charles Lorry (1726–1783) expanded upon this by following in the footsteps of Carl Linnaeus in developing a taxonomic approach to skin lesions using morphology. J. J. R. von Plenck created a system of 14 classes also based on symptoms but without a detailed stratification of subclasses within each larger grouping ( ). By this point there was much disagreement within the literature as to how to name and classify AD, as no one standard system had yet been agreed upon. As New York dermatologist L. Duncan Bulkley noted: “It is true…the fact that no less than one hundred and twenty Latin names are associated with eczema, by different writers, while the total designations applied to this eruption exceeds one hundred and eighty!” ( ).
The advent of the Bateman and Willan system and its adoption by dermatologists across the globe allowed for a shared language through which scholars in the field would be able to communicate their findings in a universal manner. Eczema belonged to the “vesicular” or bullous genera in this schema and was defined as an “eruption of minute vesicles, non-contagious, crowded together” in an anatomic distribution that covers the thighs, axilla, and perianal surfaces. Another entity in the Bateman and Willan system that resembles modern AD is porrigo larvalis willani ( ). Literally translated, this term describes a crusted mask that covers the face of the infant. These descriptions are rather fitting as the erythematous and crusting facial lesions of children with the disorder from Bateman and Willan’s time accurately depict facial AD as we know it today. Bateman and Willan believed the stimulus for these eruptions was external rather than internal, citing reports of chemicals and sunlight triggering vesicular outbreaks. It is here that their contemporaries would note the broad class of eczema encompassed a distinct entity that 20th-century dermatologists would call dermatitis venenata, or contact dermatitis. One such author, Pierre Rayer, pointed to the “ease and a rapidity” that the lesions we now know as contact dermatitis would abate after removal of the stimulant ( ).
Rayer was the first scholar to distinguish acute and chronic forms of eczema within the Bateman and Willan scheme. He describes three forms of acute eczema (eczema simplex, eczema rubrum, and eczema impetiginodes) as well as chronic eczema ( ). Rayer’s eczema simplex featured small clusters of vesicles with red patches covering large surfaces of the body. He distinguishes eczema simplex from the similarly appearing lichen simplex by noting that eczema simplex vesicles are filled with serum that oozes when punctured rather than the more solid lesions of lichen simplex that are productive of blood. Eczema rubrum is a “more intense” eruption with prominent erythema, erysipelas, red serum contained within vesicles, and irregular “jagged border.” He paints vivid descriptions of warmth and redness emanating from lesions, with the local inflammation providing a furnace for the eruptions that recur and relapse.
Tormented by pruritus of the most violent description, patients thus affected talk of nothing but heat of blood, inward fires… They cannot forget themselves in sleep; their sufferings, lulled for an instant, often return suddenly and without appreciable cause; nothing can then prevent or moderate the energy with which they begin to scratch themselves; a bloody serum flows from the torn surface of the skin; but, nothing assuaged, the pruritus continues as unbearable as before, particularly when the perineum, orifice of the vagina, or verge of the anus is the part affected; when left to itself, this cruel state often continues for months and even for years
One of Rayer’s principal contributions to the understanding of eczema was the description of natural history of the disease. He describes the scabbing of chronic eczema after vesiculopustular eruptions as well as the intriguing relapsing-remitting pattern in patients ( ). Absent, however, from Rayer’s characterization of the disease is any mention of associated asthmatic comorbidities.
Sir Erasmus Wilson, a contemporary of Rayer who also recognized the importance of the acute and chronic nature of eczema, hinted at a link between the skin findings of the disease and other elements of the atopic triad. He lectured on the association between eczema and respiratory conditions, including bronchitis. Records from a prominent American botanical remedy journal on treatments for dermatologic conditions cite lectures from Wilson near the end of the 19th century that demonstrate an understanding of the link between eczema and asthmatic conditions: “Eczema…is not infrequently associated with a similar inflammation of the mucous membrane of the air-passages of the lungs, giving rise to bronchitis” ( ). The “sudden increase of the cutaneous inflammation relieving the mucous membrane, and vice versa; and this association of bronchitis and eczema is sometimes maintained during the entire lifetime of the individual” ( ).
Wilson also contributed to a better understanding of infantile eczema, noting that children developed lesions that commonly affected “the scalp, the eyelids, the ears, particularly the backs of the ears, the integument around the mouth, the armpits, the groins, and the ends of elbows, wrists, knees, and ankles” ( ). He defines eczema as “a chronic inflammation attended with desquamation, exudation, and pruritus,” with the pruritic skin lesions becoming thick and forming “condensation of the integument” in a manner similar to the scaly lesions of psoriasis. In fact, Wilson lectured on his interpretation of psoriasis as a natural progression of eczema known as “chronic eczema squamosum” ( ). Wilson also considered pityriasis a chronic form of “exhausted eczema” after a change in the quality of skin tissue to form “excessive abundance of minute micaceous scales, and excessive pruritus” ( ). For Wilson, “nothing can be more obvious in practice than the transition of an eczema from its more active stages into the chronic condition of a psoriasis on the one hand, or of a pityriasis on the other; and only by violence can their separation be accomplished” ( ).
In Austria, the young dermatologist Ferdinand von Hebra conducted the first modern experiments establishing that a subtype of eczema developed after chemical or mechanical irritation of the skin ( ). He demonstrated that stimulation of the pubic region with the Arnica plant could yield eruptions on the face and distant regions. A passionate teacher, von Hebra also sought to train a future generation of physicians specialized in dermatology and requested the Austrian government to appoint him the title of lecturer on skin disease. He founded the Vienna General Hospital’s dermatologic service and trained multiple prominent dermatologists, including Heinrich Köebner, Carl Auspitz, and Moritz Kaposi. Dissatisfied with Bateman and Willan’s lack of an etiologic basis for classification of disease, he sought to understand the mechanisms of common skin ailments. His first great accomplishment was the publication of a paper establishing the Sarcoptes mite as the infectious cause of scabies. von Hebra was noted to state: “Never abandon a case as hopeless, but continue to study it on the basis of knowledge of its pathology and etiology until you find some way to help.” As a result of his investigations into the nature of eczema, von Hebra introduced the term mycosis sive eczema exurarum into the literature ( ). This term was not adopted in his era, but later 20th-century dermatologists would continue to explore a link with fungal infections. von Hebra’s “constitutional prurigo” featuring an infantile disease of urticarial rash with pruritic papules closely approximated contemporary accounts of infantile eczema but differed in subtle yet controversial ways. von Hebra maintained that his eponymous prurigo affected extensor surfaces as well as flexural ones, generating debate for decades about the proper place of this disease entity in the annals of dermatologic literature ( ), noting that “…in people affected by prurigo, few of the lower extremities are especially pointed in the direction of extension; it is to a lesser degree on the side of the flexion and by no means in the articular folds the pigmentation is pronounced in intense prurigo, it is not very marked in light prurigo” ( ). He also associated this form of skin disease to certain social classes, namely the poor, the Jewish, and those of lower social rungs.
In 1885, Chicago physician Henry T. Byford proposed an understanding of infantile eczema pathogenesis related to ineffective waste processing by the liver in a case series of children in the rash ( ). This theory was popular in the literature, with Chicago physician L Duncan Bulkley noting the infantile eczema rash was not linked to common irritating agents that infants commonly are exposed to, such as “irritating diaper-linen, harsh bandages” since “the disease very frequently does not get well upon removal of these irritants” ( ). Bulkley believed there was a psychosomatic trigger to outbreaks of eczema, classifying “neurotic eczema” as a subtype seen in many of his patients.
An unmarried lady, aged 53 years, was the executive officer of a charitable institution, and her duties were arduous and exacting. On Tuesday of each week she was particularly tried on account of the weekly meeting and inspection of a board of lady visitors, and that night was often sleepless. Her eczema of the face and hands was always aggravated on the succeeding morning; indeed, the eruption, which would often yield very satisfactorily to treatment during the week would burst out afresh on the Wednesday morning succeeding the visit
He also wrote of the link between eczema and asthma, noting that the comorbidity of bronchial hyperreactivity disorders in his dermatology patients suggested there was “a condition of the pulmonary mucous tract similar to that found on the skin in eczema” ( ). Importantly, he also evaluated his patients for an association between eczema and diseases of the lung parenchyma and concluded that “lung diseases cannot be said to be associated with eczema in any important manner…patients with eczema are as a rule free from lung trouble; except the asthmatic complications before alluded to” ( ). Like other 19th-century dermatologists, he distinguished between the “simple inflammation of the skin, as from heat, poison ivy, etc.” known at the time as “dermatitis” from true eczema based on history and cessation of the skin eruption with removal of the stimulus. He noted that masquerading lesions that had been used interchangeably in earlier dermatologic literature, including prurigo, which less often involves the flexural surfaces compared to eczema and seldom features “sharp, inflammatory character, and irregular distribution of papules” ( ). Bulkley’s works shed light on prognosis of different forms of eczema, with accounts of easily treatable acute vesicular eruptions and recalcitrant forms of eczema that involved the palms. Though eczema shared features of other forms of dermatitis caused by scabies and irritants, there were constitutional features Bulkley could not pinpoint that hinted at a systemic illness similar to “gout and rheumatism” rather than merely a local inflammatory reaction of the skin ( ). This final point was controversial in the literature, as an opposing school of thought held that eczema in all forms derived from a local infection of the skin rather than a systemic illness.
The mid-to-late 19th century saw the emergency of the “toxin principle” and the theory that AD was a manifestation of internal disease—much like the Hippocratic view of disease popular throughout much of Europe. Proponents of this theory, including Philippe Gaucher, believed that eczema was the manifestation of the body trying to eliminate toxins that caused various internal diseases, and attempts to treat it could lead to “driving in the disease” ( ). He believed that treatment of AD in children was especially dangerous. Louis-Anne-Jean Brocq, a French contemporary, thought it dangerous to treat lesions in those who are “aged, gouty, arthritic, or asthmatic,” noting that “in treating their eczema too energetically one may, indeed, determine the appearance of the gravest pulmonary or even cerebral congestions” ( ). Proponents of this school of thought held the prevailing opinion that AD should not be treated in most cases. However, not all contemporaries of Gaucher and Brocq agreed. opined that “eczema infantile, when left to itself, has no natural tendency to resolution or spontaneous cure; on the contrary, it merges progressively into a chronic form.”
Near the end of the 19th century some physicians were starting to place more emphasis on determining the cause and exact etiology of AD. Morris thought of AD as having either a parasitic or neurologic etiology, and he noted that the field needed to investigate the true cause of AD to guide therapeutic choices. In 1891, Brocq and Lucien Jacquet introduced “neurodermite diffuse” into the literature to describe what would become known in the English literature as the neurodermatoses. In modern medical literature these are closer to the skin-picking disorders in the Diagnostic and Statistical Manual of Mental Disorders , Fifth Edition. Brocq describes the lesions as lichenified plaques that appear at flexural aspects of the knees and elbows. They presented in two forms: disseminated and localized. Features that were characteristic of this disease of the nervous and cutaneous organ systems included neuropsychiatric symptoms such as mood lability, depression, and hyperesthesia ( ). Later, 20th-century dermatologists, including Fred Wise, note that these lesions are not histologically or morphologically consistent with true eczema and that some of Brocq’s descriptions are more in line with outbreaks of psoriasis and pityriasis rubra pilaris ( ). Nonetheless, neurodermatitis and associated terms would be used interchangeably in the literature with descriptions of various eczematous disorders by prominent authors until the consolidation of terminology in the mid-20th century.
German physician Paul Gerson Unna ended the century with a histopathologic approach to the study of cutaneous disease that sought to link all clinical features with microscopic and laboratory findings. Through histologic assessments of AD, he determined that “the essential cause of [AD] is the inoculation of a germ” ( ). Unna differentiated AD into two entities: the first resembling the rash of “staphylogenic impetigo” pathologically driven by “bacteria—the morococci of eczema” and the second appearing as “much more multiform” and due to “ever-increasing congestion of leucocytes and serous transudation” ( ). Remarkably, these findings occurred a century before the field reexamined the role of Staphylococcus aureus colonization and AD.
The 20th century
The early 20th century saw the continued exploration of old ideas and a slow convergence of overlapping definitions of AD with emerging theories of a new pathophysiology grounded in advances in allergy and immunology. Dermatologist L. Duncan Bulkley (mentioned earlier) led the American clinical research efforts with his case series of thousands of patients with the affliction. He defined “true eczema” in a 1901 manuscript as “an acute or chronic, non-contagious, inflammatory, polymorphous, constitutional disease of the skin, accompanied with itching and burning” that was distinct from the features of simple dermatitis caused by identifiable irritants such as poison ivy or mechanical abrasion ( ).
Bulkley’s theories on neurotic eczema persisted into the new century, with several investigators continuing to explore neuropsychiatric manifestations of the disease. A narrative study of 88 patients seen at Massachusetts General Hospital, including 32 with AD, found “patients with atopic dermatitis show psychoneurotic symptoms more frequently than do the patients with lupus erythematosus or normal controls” though less than the psychoneurotic group in frequency ( ). The authors noted a “definite correlation between events which evoked feelings of anger and depression and exacerbations of the eruption in the patients with atopic dermatitis” ( ).
Arthur Hall published the first major 20th-century treatise on infantile eczema in his 1905 thesis and later 1907 British Journal of Dermatology manuscript. These pieces reviewed the major theories of etiology, including the digestive school of thought, the external irritant theory, traumatic origins of eczema, the “external irritants of infancy,” the neurocutaneous theory, and “eczema as a (protective) cutaneous reaction” ( ). Hall appeared to be most intrigued by the gastrointestinal theory, noting that cases of eczema seldom occurred during the summer months when diseases of the gastrointestinal tract flourished. He drew attention to the trend of eruptions of skin irritation in his patients predominantly during the winter months. “What is generally called eczema, whether it occurs in infants or adults, is a form of reaction or response of the neurocutaneous apparatus to external irritation,” noted Hall. Chicago physician Samuel Feinberg further explored possible associations with seasonal changes, publishing a report on patients who presented with symptoms during the “mold season” between June and November ( ). Many of these patients also were allergic to several species of pollen and fungi.
At this point, the field was crowded with competing classifications and disease mechanisms, with Sutton aptly stating in his 1928 textbook, “[T]he fact remains that eczema is only a sort of dermatological scrap-heap out of which, from time to time, certain diseases that present a characteristic and definite symptomatology are extracted.” This quickly changed after a series of innovations in the emergent field of allergy and immunology, which as a term was first introduced by in 1911. An important development was the creation of the patch test assay by Joseph Jadassohn in 1895, first presented at the Fifth Congress of the German Society of Dermatology ( ).
The first major paper in the field of allergy and eczema was a case series by showing association between eczema and indigestion. The authors noted a close relationship between outbreaks of skin findings and changes in stool consistency as determined by gross and microscopic analysis. In most cases, the skin changes were very prototypical vesicular eczematous eruptions primarily affecting the head and lower abdomen. These eruptions came in two types (exudative-predominant and nonexudative processes) with the time span between prodromal symptoms and full eruptions varying from patient to patient. American pediatrician Kenneth Blackfan was inspired by these experiments and the work of Felix Mendel and Henry Lee Smith. He applied Mendel’s previously developed skin antigen assay to study whether animal proteins generated an allergic response in eczema patients. In a landmark 1916 paper, Blackfan put his theory of an eczema protein “idiosyncracy” to the test. Of subjects exposed to cutaneous injections of various animal proteins, only 1 of 43 test subjects without a history of eczema demonstrated a positive protein antigen response compared to 22 of 27 patients with eczema. He noted that “a history of eczema in early life is nearly always the rule with patients who are unable to take different foods, such as eggs, shell-fish, pork, etc., on account of urticaria and edema and sometimes asthma” whereas patients without a history of eczema rarely had positive reactions to protein antigen exposure. Chandler Walker demonstrated in 1918 that this association between eczema and allergic responses was not limited to food protein but also applied to proteins obtained from horse dandruff, ragweed, and pollen. noted that a small amount of externally or internally applied proteins paradoxically improved the disease symptoms in eczema patients, though past a certain threshold exposure to increasing amounts of protein exacerbated the disease.
first adopted the term atopy in the medical literature after consulting philologist Edward Perry for help in describing a pathologic entity that was appropriately deemed “strange” in Greek terms. They explicitly defined several features of the peculiar nonanaphylactic type of hypersensitivity reaction known as atopy, including the characteristic of being “greatly lessened but not completely removed by the suitable injection of the active substance.” Though atopy shared features with anaphylaxis and infectious hypersensitivity, all three types of reactions were clearly distinct from “non-antigenic” reactions of dermatitis venenata caused by irritants such as poison ivy ( ).
Sulzberger and Wise developed the first modern definition of AD. Nine features listed by the authors included a family history of atopy, prior infantile eczema, locations of skin lesions at the elbow and knee flexural folds as well as neck, chest, and face, gray-brown lesions, no true vesicles, irritability with vasomotor agitation, negative patch test results, positive prick tests and intradermal tests, and serum positivity ( ). Five years later developed their own list of diagnostic criteria, including family history of allergy, association with reaction to specific foods, age at onset, and stereotypical location of skin lesions that included ankles, wrists, and cheeks. These pioneering experiments demonstrated that certain substances could provoke the eczematous reaction in individuals with a predisposition. In a 1939 review, Feinberg declared “atopic dermatitis” was now the commonly accepted term in the literature for what had formerly been known by a variety of names ranging from neurodermatitis to eczema. published lectures contained very familiar descriptions of the disease entity appearing first in infants and affecting the antecubital and popliteal fossa, wrists, and face all with positive responses to the Prausnitz-Küstner antibody test. Interestingly, Wise and Wolf continued to use separate terms to define infantile eczema from AD despite noting that the two disease forms only differ in subtle ways while sharing the same broad clinical and histologic traits.
Toward the latter 20th century, researchers strived to develop precise and replicable methods of diagnosing AD. The fruit of these labors was a set of criteria from Hanifin and Rajka published in 1980 that defined AD as requiring at least three of the following major features: pruritus, flexural lichenification or linearity in adults, facial and extensor involvement in children, chronic or chronically relapsing dermatitis, and a personal or family history of atopy. It required at least 3 of 23 originally defined minor features as well ( ). These criteria were further honed by the UK Working Party in 1994, who validated their diagnostic criteria through a study of patients from nine centers. Their criteria required itchy skin in addition to three of the following five criteria: history of involvement of the flexor skin folds, personal history of atopy (asthma or allergic rhinitis), generally dry skin in the last year, visible flexural eczema, and onset under the age of 2 years (for children ≥4 years) ( ). The UK Working Party’s criteria have been validated in other populations ( ) and have since become the de facto standard for diagnosis of AD today.
Historical approaches to the treatment of eczema
Hippocrates approached treatment of dermatologic disease with the philosophy that the opposite of what the lesion’s characteristics were should be applied as a counterbalance (e.g., for moist lesions he would prescribe a drying agent and for dry he would suggest an emollient) ( ). Hippocrates was also a proponent of the humoral approach to medicine (i.e., the theory that human disease is the result of imbalance of the four humors: blood, phlegm, yellow bile, and black bile). Practitioners of the humoral theory believed that AD was the body’s attempt to right any imbalances in the four humors, and thus interventions could only interfere with the healing process. This theory continued to influence many 19th-century dermatologists, particularly French physicians such as Alibert, Brocq, and Gaucher ( ). The French school of dermatology viewed treatment of eczema as “constitutional,” involving multiple modalities, including but not limited to medicine, diet, and exposure to the outdoors ( ).
Erasmus Wilson was an early advocate of treatment of AD and other cutaneous pathologies, breaking from the humoral approach to medicine that was popular in his time. He differentiated cutaneous diseases into acute and chronic forms, providing different treatments for these different forms. For chronic AD, he applied his “law of treatment of cutaneous disease,” which contained three key principles for the treatment of infantile eczema: “elimination, restoration of power, and alleviation of local distress” ( ). For elimination, he recommended a solution of calomel (see later for discussion) with white sugar or milk; for alleviation of local distress, he recommended “benzoated ointment of the oxide of zinc”; and he recommended arsenic as a last step for the somewhat oddly termed “restoration of power.” von Hebra was another early advocate of treatment of AD; he suggested the use of treatments such as “oily or fatty [emollients]” and would add “mercury, zinc, lead, copper, iodine, arsenic, sulphur… [or] tar in cases of eczema” ( ). Though tar was used by many 19th- and early 20th-century dermatologists dating back two millennia to Dioscorides, it was not systematically studied as a treatment modality until Downing and Bauer’s landmark 1948 paper characterizing 600 subjects receiving tar for eczema and psoriasis. They compared coal tars of different types and manufactured at different temperatures, noting that all performed with roughly similar clinical efficacy ( ). By the mid-20th century, tar was deemed to be an effective adjunct treatment for AD. Tar was viewed favorably for subtypes of “dry sluggish” eczema and continued to be prescribed well into the modern era.
Around the same time, developed a threefold principle of treatment with the components of “regimen, rest, and time.” He was rather conservative with prescribing medication, noting that many mild cases of eczema simply resolved after “changing the nurse” who was attending the patient on the ward or following a sudden change in a person’s diet ( ). Rather skeptical of many concoctions used by his contemporaries, he appeared to adopt a “do no harm” strategy for mild cases. Among his treatment arsenal were emollients for localized lesions, soothing ointments such as oxide of zinc and protochloride of mercury for “furfuraceous” or flaky lesions, and blood-letting for severe eruptions of eczema rubrum ( ). describes a case series of infantile eczema eruptions of the scalp treated with topical calomel. Calomel, or mercury(I) chloride, was popular in 19th-century medicine in the United States and England for a variety of illnesses, including syphilis, gout, tuberculosis, and malignancy. Unfortunately, high doses of oral calomel led to severe side effects of mercury poisoning, including stomatitis and gastrointestinal complaints of vomiting and bloody diarrhea ( ). In the tradition of the French school of dermatology, also noted that in many cases “a properly regulated diet is necessary, and in some cases is all that need be recommended.”
At the start of the 20th century, dermatologic textbooks contained lengthy lists of tinctures and remedies for controlling symptoms of AD. Arsenic was a popular agent used in severe cases of infantile eczema. noted the “almost specific control which arsenic will have over eczema in small children,” but also noted “it seems to have less effect on the disease after the age of 5 years.” stated a “tumblerful of milk, slightly warmed, one hour before each meal, followed if possible, by a rest of half an hour in a darkened room” was efficacious for AD, and particularly in neurotic eczema. He also wrote of topical, “local” treatments, including Lassar paste (composed of zinc oxide) and gelatin-glycerin preparations, which were often added to camphor, salicyclic acid, or resorcinol—common therapies used in many cutaneous ailments at the time. Other topical compounds such as picric acid and potassium permanganate were noted to provide relief of pruritus with AD ( ).
Later works by Morris contradicted Bulkley’s work, stating “[one must] clear one’s mind of the notion that arsenic or any other drug is specific” to AD ( ). He categorized treatments as internal remedies or local therapies and recommended tailoring treatments to the individual’s disease rather than the use of static treatment regimens for all patients. Among internal treatments, recommended antimony, calomel, quinine, strychnine, ergot, belladonna (atropine), and sedatives such as opium, along with light clothing and “complete rest, both of mind and body.” For local treatments, he recommended the use of creams and pastes containing ingredients such as salicylic acid, zinc oxide, and petroleum jelly, only after the “removal of all crusts and scales that prevent the free access of the remedy to the seat of the disease” ( ). Other physicians, such as Henry Boenning, recommended the use of topical treatments for AD. He detailed a case of a young patient successfully treated with “sulphur ointment with carbonic acid to be applied twice daily over the thickened skin and the papules, preceding the application by a hot bath” ( ). For pruritus refractory to arsenic, recommended exposing the afflicted lesion to roentgen rays as a last resort.
Despite 20th-century progress in understanding the link between allergy and eczema, food and antigen-based treatment modalities were noted by early dermatologists to be ineffective. conceded that “little can be done to influence the atopic state” by targeting specific allergens that triggered disease flares in patients. wondered if this puzzling nonresponse phenomenon suggested a missing link in the atopy theory as a whole, asking “is it not logical to assume that the general concept of allergy is probably correct but that the specific exciting cause is missed?”
Despite a careful examination of the history of eczema, it remains unclear whether many of the trends over the centuries in classification reflect changes in nosology and disease understanding rather than actual changes in the entity itself. It is possible that, like cultures, languages, and species, diseases undergo alterations over time, such that our modern version of eczema may differ significantly from what was described millennia ago. It may also be the case that with changes in lifestyle and available therapies, the contemporary milieu significantly alters the presentation and natural history of some diseases.
Regardless, an undeniable—if bumpy at times—progression toward a broader and deeper understanding of eczema is now evident. Particularly in the past few decades, we have witnessed an explosion in both scientific understanding and therapeutic innovations, built on the long and fascinating history of this persistent, itchy malady.