Elementary Lesions Research Articles

Robert Willan and the French Willanists.

In 1798, Robert Willan published the founding textbook of British dermatology. In adopting the elementary lesions principle previously described by Josef Plenck and improving the nomenclature of the skin diseases, Willan established a method for the diagnosis and a doctrine for the nosology of the cutaneous diseases. Introduced into France by Biett in the 1810s, the Willanist method, which allowed diagnosis on the basis of objective criteria, was adopted by the majority of the dermatological community. However, as a doctrine, Willanism, the use of elementary lesions as a framework for classifying diseases, became the subject of lasting debate. In fact, apart from a few, most leading French dermatologists did not accept Willan's doctrine and preferred classifications according to systems which were supposed to reflect the best understanding of the cutaneous diseases: physiological, aetiological and pathological. Willanism is still used by every dermatologist as a method for recognizing skin diseases. It constitutes a firm link to the founding period of modern dermatology and remains a bastion against uncertain hypotheses.

Clinical and biochemical expression of the histopathological lesions of primary biliary cirrhosis

Background/Aims: This study aimed to assess the relationships which may link elementary histological lesions with symptoms and biochemistries in primary biliary cirrhosis. Methods: We studied 103 patients with primary biliary cirrhosis who participated in a double-blind, placebo-controlled trial of UDCA treatment and in whom liver biopsy specimens obtained at entry were reassessed. Relationships between histological features, fatigue, pruritus and biochemistries were calculated by using exact tests for 2 ordinal variables. Results: The degrees of severity of fatigue and pruritus were significantly and exclusively related to the presence of florid interlobular bile duct lesions ( p<0.01 and p<0.02, respectively). The only laboratory parameter associated with the presence of interlobular bile duct florid lesion was IgM level. The most discriminant biochemical test for interlobular bile duct paucity was gamma glutamyltranspeptidase activity. The degree of severity of both lymphocytic hepatocellular piecemeal necrosis and lobular inflammation and necrosis was mainly associated with increased gammaglobulin and IgG levels and to a lesser extent with increased IgM and aspartate aminotransferase levels. The extent of fibrosis was mainly associated with gammaglobulin levels and to a lesser degree with serum albumin, bilirubin and IgG levels. Conclusions: Symptoms and biochemistries classically used to assess primary biliary cirrhosis reflect in part the degree of severity of the main elementary histological lesions. We propose that the picture of primary biliary cirrhosis results from the clinical and biochemical expression of three distinct processes, e.g., bile duct inflammation and destruction, parenchymal inflammation and necrosis, and fibrosis. The various combinations of these processes may explain why the spectrum of primary biliary cirrhosis varies from typical primary biliary cirrhosis to mixed type of primary biliary cirrhosis and autoimmune hepatitis and suggests that the response to therapies may depend on the predominance of each process in a given patient.

Rheumatoid arthritis: follow-up and response to treatment

Objective: To assess the role of diagnostic imaging techniques in the identification and follow-up of the anatomical damage induced by the chronic inflammatory process of rheumatoid arthritis (RA) not only to study the natural history of the disease but also and especially to assess the long-term response to disease-modifying anti-rheumatic drugs (DMARD). Materials and methods: The relative literature data were reviewed and compared with our personal experience with different imaging modalities such as conventional radiography (CR), ultrasound (US) and magnetic resonance imaging (MRI). Results: Several radiologic techniques have been used over the years to study articular damage in RA: they describe and quantify the articular damage (semi-quantitative analysis) based on a series of parameters and elementary anatomical lesions which are given a rising score. For its sensitivity in detecting early disease signs and the possibility to express anatomical damage progression quantitatively, Sharp's index is considered the best tool for evaluating RA patients. The close correlation between clinical parameters and the radiologic scores obtained regardless of the method applied led to a new concept of anatomical damage related to the 'radiologic progression of the disease' which is a more precise measure of RA severity than the single isolated radiograph. The progression of radiologic damage in rheumatoid arthritis is expressed as the number or proportion of new eroded joints/year: independent of the index adopted and the terms used to express progression, severe radiologic damage occurs in the early disease stage, involving approximately 2% of the joints within about 1 year, and 13% within 2 years, with an estimated average annual progression of 1.3%. Radiologic techniques evaluate the anatomical damage in the course of RA only with reference to the osseous component of the joint and therefore apply to a disease stage that is largely irreversible. MRI and US detect the soft-tissue damage occurring in the earlier phases and are more likely to respond to early treatment. The former technique appears to be useful to detect soft-tissue damage like synovial pannus, intra- and periarticular and peritendinous effusion, capsuloligamentous articular and tendon changes. Its high sensitivity for minimal bone erosions and chondromalacia has been demonstrated. US allows to demonstrate a wide range of soft-tissue changes of the hand and wrist. Joint-cavity widening, loss of cartilage definition, bone erosions, widening of flexor tendon sheath and tendon structure are also well depicted on ultrasound images. Conclusions: CR is the central tool in the diagnosis, staging and follow-up of RA patients and in general in the assessment of treatment efficacy; MRI and US are complementary tools.

High intensity focused ultrasound—potential for cancer treatment

The prospect of being able to use "minimally invasive" surgical techniques is of great interest today, particularly for reasons of health economics, patient acceptability and reduced morbidity. High intensity focused ultrasound (HIFU) has long been known to offer the potential of very precise "trackless lesioning" but has only recently, with the advent of high quality methods of medical imaging, become a practicable possibility. High intensity beams can readily be achieved using either bowel or lens focusing procedures and, by choice of a suitable acoustic frequency, regions of tissue destruction--"lesions"--can be induced at depths of up to at least 10 cm with exposure times of the order of 1 s. Theoretical and experimental evidence indicates that the primary mechanism of damage is thermal, i.e. "cooking" of the tissues. Both conventional cavitation and boiling of tissue water may complicate the situation. Furthermore, substantial non-linear behaviour is involved. On histological appearance the lesions have a spatially sharp demarcation between regions of normal and dead cells. When attempts are made to ablate a block of tissue, by creating an array of adjacent elementary lesions, a phenomenon is observed of inhibition of formation of a lesion whose placing is too close to that of a neighbour. Provided that this problem is dealt with, complete ablation of an extended block of tissue can be achieved. For animal tumours in particular, this observation is reinforced by evidence both of in vitro cell survival and of tumour growth delay experiments. Clinically, the sites accessible for HIFU treatment will be limited by the need for a suitably wide acoustic window that either is available naturally or can be provided by a relatively minor surgical procedure. Tumour sites which thus offer a realistic prospect for local control (and some of which are already the subject of phase 1 trials) include liver, bladder, kidney, prostate, breast and brain. There is also considerable interest in non-cancer applications in these and other sites.

Blistering eruptions caused by drugs: Commentary

C onsumption of drugs is increasing worldwide. The greater it becomes, the more physicians have to reckon with unexpected side effects. Among the untoward drug reactions, the cutaneous ones are the most obvious and often worry both doctor and patient more than other, possibly graver conditions. In addition, continued progress in the development of therapeutic agents and protocols poses difEculties for the dermatologist who faces the increasingly complex task of identifying, evaluating, and treating new adverse cutaneous reactions. This has prompted the publication of interesting monographs and books devoted entirely to cutaneous drug reactions. An issue in this journal dealing with “Unexpected Drug Reactions” l and the book Adverse Drug Reactions and the Skin2 are very good examples of the increased interest in this matter. Lately, bullous drug eruptions seem to predominate -not only the blistering eruptions classically related to drug intake (eg, fixed drug eruption, Stevens-Johnson syndrome, toxic epidermal necrolysis), but also certain bullous conditions usually thought to be idiopathic diseases (eg, pemphigus, bullous pemphigoid), for which a growing body of evidence points to the possible and not exceedingly rare induction by drugs. In fact, reports of pemphigus (or pemphigus-like syndrome) induced or triggered by drugs have increased so much in the last few years that today dermatologists are advised to consider a medicamentous origin whenever they observe pemphigus. The increased frequency of these unusual blistering eruptions may be connected with the widespread use of potent new drugs that, in certain conditions, are capable of causing intraepidermal or dermoepidermal detachment with or without immune medication.3 In this issue of Clinics in Dermatology, a panel of experts have been selected to report on a range of topics from certain misleading clinical aspects to possible pathomechanisms involved in blistering eruptions linked to drug intake. In particular, this issue stresses the crucial importance of close cooperation between clinicians and biologists and of a multidisciplinary approach in recent advances as well as in future research concerning cutaneous drug reactions. The fascinating article by Emiliano Panconesi on Historical Aspects reminds us that blister eruptions are less cited in the ancient literature than other elementary morphologic lesions. The great Alibert’s famous treatise arranged almost all the blistering eruptions into the First Order (“eczematous dermatoses”) and Third Order (“tineas”). Dealing with the epidemiology of bullous drug reactions, Stephen M. Breathnach and William G. Phillips note that patients with human immunodeficiency virus (HIV) infection or full-blown acquired immunodeficiency syndrome (AIDS) appear to be at markedly increased risk for bullous drug eruptions, especially those caused by sulfonamides, particularly co-trimoxazole (trimethoprim sulfamethoxazole). Narciss Mobini and A. Razzaque Ahmed superbly demonstrate how cutaneous reactions to drugs are modulated by the genetic background and immune status of the host. This may well explain the great clinical variety of eruptions reported after drug intake. Gianni Angelini, Gino A. Vena, Mauro Grandolfo, and Mario Mastrolonardo cover the wide field of iatrogenic contact dermatitis and eczematous reactions, a heap of clinical problems that no dermatologist can help coping with daily. An interesting observation on this topic is that highly sensitizing substances may be associated with a low incidence of allergies simply because they are little used in clinical practice (eg, mercury), whereas substances with a low or moderate sensitizing power may be very common causes of contact dermatitis because of their wide use (eg, neomycin). With respect to fixed drug eruption, Paolo Lisi and Luca Stingeni report some interesting data, including the fact that the inflammatory re-

Fine structure of hepatic sinusoids and sinusoidal cells in disease

Liver sinusoids are special capillaries that are limited by fenestrated endothelial cells, without a genuine basement membrane, surrounded by perisinusoidal cells storing vitamin A, and harbouring Kupffer cells and pit cells, resident macrophages, and large granular lymphocytes, respectively. Each nonparenchymal cell and parenchymal cell of the liver interacts with all others and with the extracellular matrix. Therefore, the functional ability of each cell is constantly being modified by the metabolic activity of the others. Human liver biopsies (132), needle or surgical, perfusion-fixed with glutaraldehyde and processed for transmission electron microscopy (TEM), and occasionally for scanning electron microscopy (SEM), were examined. The study included liver diseases (such as alcoholic liver diseases, benign and malignant liver tumors, cholestasis of various origins, fulminant hepatitis, acute rejection after orthotopic liver transplantation, Budd-Chiari syndrome), as well as general or extrahepatic diseases (such as diabetes, hemochromatosis, hypervitaminosis A, various hematological disorders), and normal controls. Ultrastructural abnormalities are described and illustrated under two different headings: 1) elementary lesions of sinusoidal cells (endothelial, Kupffer, perisinusoidal and pit cells), nonsinusoidal cells (in the space of Disse and/or in the lumen), the extracellular matrix; and 2) the major pathological entities including perisinusoidal fibrosis, capillarization of sinusoids, sinusoidal dilatation, and peliosis. In the discussion, an overview of the major abnormalities reported in the literature is presented, and some specific questions regarding 1) perisinusoidal fibrosis in liver with normal histology, 2) the overload of perisinusoidal cells with lipids in non-hypervitaminosis A intoxication and 3) the etiological relationship of sinusoidal dilatation, peliosis, perisinusoidal fibrosis, or sinusoidal tumors with drugs and toxic compounds are discussed. In the event that lesions are not specific to any diagnosis, the knowledge of the ultrastructure of sinusoids is extremely useful from the perspective of the liver as an ecosystem.

Porokeratosis Punctata Palmaris et Plantaris

Seven members from three generations of a Saudi family presented with porokeratosis punctata palmaris et plantaris (PPPP). In our series of patients, the disorder began in their early 20s, seemed to be transmitted as a dominant trait, and affected males only. The elementary lesion was a tiny keratotic spine, and the involvement was strictly limited to the volar aspects of the hands and to the soles of the feet. Histological studies showed a columnar parakeratosis that resembled the cornoid lamella of porokeratosis, but other clinical and histological traits tended to make PPPP an entity that was distinct from true porokeratosis. There have been only six reports in the literature on genuine PPPP before this series.

Lymph Node Modification in Patients with the Acquired Immunodeficiency Syndrome (AIDS) or with AIDS Related Complex (ARC): A Histological, Immuno-Histopathological and Ultrastructural Study of 45 Cases

The authors present the results of a histopathological study on the lymph-nodes taken from 45 subjects suffering from either an AIDS or from a chronic adenopathy corresponding to the definition of AIDS related complex (ARC). The various aspects observed were classed as type I to type IV. The lymph-node modifications observed in the 29 patients with an ARC could be divided into three principle groups: an extensive follicular hyperplasia associated with other elementary lesions or type IA (25 lymph-nodes from 23 patients); changes resembling a multicentric Castleman syndrome or type IB (1 case); angioimmunoblastic-like (AIL) lesions or type II (2 cases) and an association of lesions of type II (7 lymph-nodes from 6 patients). During AIDS, the adenopathy usually disappears, and the small lymph-nodes removed, especially on autopsy, show an extensive lymphoid depletion (type III) with systematic sclerosis (15 lymph-nodes from 14 patients). When adenopathy persists, it is due to infections complications (tuberculosis, cryptococcosis, avian mycobacteriosis and Whipple's disease like lesions). Of the 10 patients in whom a Kaposi's sarcoma was observed, only 6 showed lymph-node involvement, or type IV. The different histopathological lesions seem to appear according to an evolving succession, proven by certain association of lesions and by successive biopsies. In our series, 17% of subjects with an ARC evolved to AIDS. Lymph-node biopsy allows a possible ARC to be implicated on the association of the following simple lesions: follicular hyperplasia with partial or total destruction of the perifollicular lymphocytic cisterna, infiltration of the germinative centres by streams of small lymphocytes, evolving to an aspect of a "burst" germinative centre and various sinusal reactions with, in particular, the presence of neutrophilic polynuclear cells. The biopsy also allows the forms with bad prognosis to be recognized: those with AIL-like aspect or multicentric Castleman-like syndrome, which seems to represent a particular evolutive form. Finally, it also detects, in certain cases, the localization of a Kaposi syndrome, signalling the passage to AIDS. The immunopathological studies present a double interest. Firstly, they offer arguments in favour of the diagnosis: increase in the number of T8 lymphocytes in the germinative centres with the formation of small clusters and disruption of the network of dendritic reticular cells, and the inversion of the T4/T8 ratio in the extra-follicular cortical regions, by either a decrease in T4 lymphocytes or by an increase in T8 lymphocytes.(ABSTRACT TRUNCATED AT 400 WORDS)

Structural hepatic changes associated with cyanamide treatment: cholangiolar proliferation, fibrosis and cirrhosis.

The authors present the clinical and histological findings in a series of 42 liver biopsies from 39 chronic alcoholics treated with cyanamide as aversion therapy. All biopsies displayed characteristic cytoplasmic inclusions in the liver-cells. Fibrosis and disruption of the parenchymal-connective tissue interface were observed in all cases. According to the severity and extension of fibrosis, three stages could be depicted: Stage I. Periportal activity cholangiolar type (ACT), which is defined by cholangiolar proliferation, fibroblastic activation and inflammatory infiltrate, which together cause a blurred appearance of the parenchymal-connective tissue junction. It is the elementary lesion and was observed alone in 26 biopsies. Stage II. Portal-to-portal linkage. It was observed in 10 biopsies, all of which also showed periportal ACT. Three of these came from patients with two biopsies in which transition from stage I (first biopsy) to stage II (second biopsy) was observed. Stage III. Nodular parenchymal regeneration, associated with changes observed in stage I and II. It was found in six patients. The histological picture resembles the biliary type of cirrhosis. There is a clear-cut correlation between the length of treatment and the stage of the hepatic lesion.

Transient Acantholytic Dermatosis

Six patients with an apparently unique, self-limited, primary acantholytic skin disease are described. The elementary lesions were pruritic, discrete, edematous papules or vesiculopapules which tended to appear first on the trunk, possibly as a Koebnerlike response to nonspecific irritation, such as ultraviolet light. The two youngest patients, aged 46 and 48, developed only localized manifestations which disappeared in a few weeks. The older patients, ranging from 56 to 74 years old, had disseminated eruptions which lasted several months. Although there was a strong histologic resemblance to Darier's disease in three cases, and to Hailey-Hailey's disease in the other three, clinical considerations seem to rule out both of these diagnoses. It is stressed that cytologic examination is most useful in recognizing the disease.

Pathogenesis of acne vulgaris. I. Comedogenic properties of human sebum in external ear canal of the rabbit.

Scalp sebums of 64 young men were applied once daily for ten times to the external ear canal of the rabbit. In every instance follicular hyperkeratosis resulted. This finding supports the conception that sebum contains substances that directly stimulates the follicle to form a comedo, the elementary lesion in acne vulgaris.

Pathogenesis of Acne Vulgaris

Scalp sebums of 64 young men were applied once daily for ten times to the external ear canal of the rabbit. In every instance follicular hyperkeratosis resulted. This finding supports the conception that sebum contains substances that directly stimulates the follicle to form a comedo, the elementary lesion in acne vulgaris.

Identification of urate crystals in gouty synovial fluid.

Excerpt Urate crystals have been noted in synovial fluid from gouty patients in the past, but this finding was believed to be infrequent and of little assistance to the clinician in his attempt to ...

Monoporous and polyporous acne.

A comedo, or blackhead, may be defined as a plug of sebaceous material found in a duct of a sebaceous gland. It is most commonly seen as the elementary lesion of acne vulgaris, but it may also be present in linear nevi, postradiation atrophy, hidradenitis suppurativa, and tar acne.1-3 A single comedo may have more than one opening on the skin. The term double comedo'' (Ormsby, as quoted by Ormsby and Montgomery4) was used to describe a comedo having two openings which were connected beneath the skin (Fig. 1b). No name was given to the comedo which had more than two openings on the skin. The term grouped comedones'' (Fig. 1e) is used to describe a patch of numerous blackheads, each of which has a single opening on the skin (Thin, as quoted by Ormsby and Montgomery). A giant comedo (Fig. 1g) describes any huge blackhead

Atlas clinique d'ophthalmoscopie photographique.

As photography of the eyeground has made great advances, the authors believe that an atlas of photographic pictures of the fundus oculi would be suitable for young ophthalmologists and general practitioners to learn that the elementary lesions in pathologic conditions of the fundus are comparatively simple and conform to similar changes encountered in general pathologic conditions. The apparatus used is the well known Nordenson camera. The great advantage of photography of the fundus, as has been stated before, is that successive pictures will describe the course of a lesion and at the same time give exact measurements of the lesion, while the drawings in color of the older atlases lack the exactness of a good photograph. The photographs were obtained during ten years' attendance at the clinic of Dr. Bailliart at the Quinze-Vingt, and a number of others have been added through the courtesy of Amsler, Bailliart, Diaz-Caneja, Laignier, Mawas,

HEMATOGENOUS CUTANEOUS TUBERCULOSIS (SARCOID) IN NEGROES

Hematogenous cutaneous tuberculosis in the Negro seems to conform in general with the various manifestations of such disorders in the white race. The relative incidence seems to be much greater as judged from the relative frequence in Negroes at the Central Free Dispensary and the increasing number of reports of cases and clinical articles dealing with these disorders in Negroes. A general review of the pathologic peculiarities of tuberculosis in the Negro by Pinner and Kasper 1 seems to explain this, as they found hematogenous metastases, exclusive of miliary tuberculosis, more than twice as often in the Negro as in the white race in a series of over 500 autopsies on both races. If this is true of tuberculosis in general, why should it not be true of hematogenous cutaneous tuberculosis? In the series of 6 cases to be described here the elementary lesion varied from a small lichenoid papule

AMERICAN DERMATOLOGICAL ASSOCIATION

A Case for Diagnosis. Presented by Dr. Stokes. A woman, aged 24, single, had an eruption of three years' duration which had been treated as psoriasis. The elementary lesion was apparently a miliary pustule (follicular?), with peripheral extension to a pansy-shaped lesion, peripherally bullous or vesicopustular, with a hard, dry central crust. Healing usually occurred without but sometimes with slight scarring. The eruption had been limited to the flanks, back and axillae, but recently it had appeared on the abdomen. The patient also had epidermophytosis of the toes, with a questionable involvement of the anal cleft and axillae. The Kolmer reaction on the blood had been repeatedly negative; the results of the Kahn test was O11 on two occasions. Bacteriologically, Staphylococcus citreus was found. The eruption had responded temporarily to roentgenotherapy (10÷5 treatments, the last of ¼ HSD each). It had cleared once under treatment with vaccine of Staphylococcus citreus