Eponyms and clinical entities from the land of Israel.

Seven eponyms have been pioneered by dermatologists in Israel: Brenner's sign, Chanarin-Dorfman syndrome, granulated sweetener packet sign, isopathic phenomenon of Sagher, lanolin paradox, Nakar-Ingber disease, and Wolf's isotopic response. In addition, there are three id reactions described by Israeli dermatologists: leishmanid, pediculid, and scabid. There is also the acronym PEMPHIGUS, which stands for the causative reasons for pemphigus. We celebrate these eponyms and clinical entities, which reflect the impressive progress made by dermatologists in Israel during the past century who have helped to build an academic, vibrant, and dynamic specialty in the Holy Land.

The Granulated Sweetener Packet Sign.

The last two decades have seen a continuing shift from visual and tactile diagnoses in dermatology towards novel, state-of-the-art, and noninvasive instrumental technologies. Against the current tide toward replacing classical physical examinations with sophisticated high-tech ones, the present article will describe an easy-to-use and practical clinical sign to differentiate between metastases of malignant lesions and apparently benign inflamed/infected dermoid cysts. Epidermoid cysts (sometimes erroneously called "sebaceous cysts") are subcutaneous nodules containing keratin and encapsulated by an epidermoid wall. They are mobile nodules, smooth to the touch, variable in size, and most commonly located on the face, neck, and trunk. They may rupture or become infected and inflamed, red, painful, or purulent. Diagnosis is usually clear-cut, and uncomplicated cysts may not require treatment. Patients usually seek advice and request excision for esthetic or medical reasons (inflammation/infection). A 48-year-old otherwise healthy woman presented for a consultation because of a small cyst on her forehead (Figure 1). Two-finger palpation of the cyst revealed that it did not have the gelatinous fluctuant consistency of an ordinary cyst, but rather felt like a packet of granulated sweetener. The histological diagnosis of the cyst was small-to-medium-sized T-cell lymphoma. The diagnostic challenge of this case was to distinguish between metastases and an ordinary innocent-appearing cyst. The impression of a packet containing granular material upon palpitation of a cyst can be the definitive clue to detecting metastases of malignant lesions among what appear to be uncomplicated dermoid cysts. We have seen several such cases of subcutaneous nodules that turned out to be metastases of sarcomas and carcinomas, all of them with the same impression of a packet of granulated material upon palpation. We propose the term "granulated sweetener packet sign" for this diagnostic sign.

The rash that presents as target lesions.

We have explored the rash that appears as target lesions, with the central and dominant diseases belonging to the Stevens-Johnson syndrome/toxic epidermal necrolysis group. After presenting the clinical patterns of an individual target lesion and classifying them into different types of lesions, the contribution has been organized with groups characterized by such specific findings according to the type of lesion: flat or raised, typical or atypical, presence or absence of fever, presence or absence of mucosal ulcerations, presence or absence of arthralgias, and/or internal organ involvement. Other specific features, such as histologic appearance, immunofluorescence findings, and laboratory changes, are considered. We provide clinicians with an algorithmic, systematic, and logical approach to diagnose the condition of the patients who present with targetoid lesions, and enable them to differentiate between those with serious systemic and life-threatening diseases from others with ordinary skin ailments.

The life-threatening rash of poisoning.

Dermatology is frequently viewed by physician and surgical colleagues as a specialty with few emergencies. Although the majority of dermatology practice is in the office setting, cutaneous emergencies do occur through referrals from primary care and as ward consults. Even though cutaneous signs of poisoning would be an uncommon emergency consultation, it is important for dermatologists to be aware of the clinical presentations so as to be able instigate appropriate time critical treatments.

Drug eruptions in the mature patient.

The world's population is now ageing at an unprecedented rate. Declining fertility and improved health and longevity have generated rising numbers and proportions of the older population in most parts of the world. With advancing age, however, comes an increasing incidence of disease (comorbidity or multimorbidity), an increasing use of medications (polypharmacy), and consequently an increase in adverse drug reactions (ADRs). Age-related changes in pharmacodynamics and pharmacokinetics (eg, volumes of drug distribution, metabolism and clearance, altered drug responsiveness and toxicity) and greater vulnerability to ADRs are other reasons for the higher incidence of ADRs in the elderly compared with young adults. Because the clinical patterns of ADRs are very similar for all age groups, including the elderly, the present review will deal mainly with statistics and numbers, rather than the clinical and/or disease patterns.

"Wolf's isotopic response": the originators speak their mind and set the record straight.

Having been the first to have introduced the concept of "isotopic response" three decades ago, we wanted to express some of our thoughts on its current application, now that more than 100 such cases have been reported in the literature. It is, of course, gratifying to read about its appropriate application, and it is our hope that others will refrain from distorting its original meaning.

The Pathergy Test as a Diagnostic Tool.

The pathergy test produces a nonspecific hyperreactive lesion in Behçet's disease (BD), a finding that has been known since 1937. Pathergy refers to the development of new skin lesions or the aggravation of existing ones after trivial trauma. In clinical practice, the pathergy test induces a skin response by needleprick, with positive reactions manifesting as a papule or pustule developing by 48 hours. The pathergy test is one of the major features and diagnostic criteria of the disease. It is very similar to the erythematous papules or pustules that appear spontaneously in patients with BD. There is no standardized method for conducting the pathergy test. Intradermal, intravenous, and subcutaneous applications are used. There is no generally accepted opinion on which form of the test yields a higher positivity rate. The pathergy reaction is also reported in pyoderma gangrenosum, and has been noted in other neutrophilic dermatoses such as Sweet syndrome. The overall objective of this contribution is to provide a review of the available information, literature, and research relating to the pathergy test.

Occupational acral dermatitis and where the twain shall meet.

This contribution, which is somewhat of a departure from the usual format, will focus on dermatologic conditions that are consequences of the patients' choices of employment, hobby, or even other forms of recreation. Most of the cutaneous changes involve the hands and feet, and each is labeled according to the anatomic location.

Acral manifestations of Sweet syndrome (neutrophilic dermatosis of the hands).

Neutrophilic dermatosis of the hand (NDH) is a rare localized variant of the syndrome, originally described two decades ago by Strutton et al. The lesions of NDH and Sweet syndrome are similar, as indicated in the first report of NDH. Both diagnoses are characterized by an acute onset of fever, leukocytosis, and tender, erythematous infiltrated plaques. There are also bullae and ulceration in NDH, in contrast to Sweet syndrome, in which bullae are quite uncommon, especially at the early stages. Similar to Sweet syndrome, the majority of NDH patients are women (69%). Patients with NDH present with fever, peripheral neutrophilia, leukocytosis, and/or an elevated erythrocyte sedimentation rate or C-reactive protein level, but at a significantly lower rate than those in Sweet syndrome (33%). Similar to Sweet syndrome, NDH has been associated with the following conditions: Malignancies (particularly hematological [21%], most common of which is acute myelogenous leukemia, but many other malignancies as well), inflammatory bowel disease (19%), medication and vaccination-related eruptions, bacterial and viral infections, rheumatologic diseases, and others. The clues to the diagnosis of NDH are the same as for Sweet syndrome. Awareness of this diagnosis is important not only to avoid unnecessary medical and surgical therapy and to expediently initiate the administration of steroids for this highly responsive dermatosis, but also to conduct an appropriate workup to exclude associated diseases, especially malignancies.

Inflammatory Lipid Mediators in Common Skin Diseases.

Lipid mediators play a main role in the complex course of cutaneous inflammatory reactions. They regulate a wide spectrum of cellular processes such as cell proliferation and apoptosis. In the early phase of inflammation, excessive amounts of lipid mediators are released and play a major role in the pathogenesis of skin diseases. Recent data suggest that lipid mediators are able to interfere with the pathogenesis of certain dermatologic diseases, seriously affecting patient quality of life. Acne, psoriasis, and atopic dermatitis are specific examples of skin diseases that may respond to treatment with medication affecting these metabolic pathways. The authors briefly present the current knowledge about the role of lipid mediators in common skin pathologies.

Bacterial infections of the folds (intertriginous areas).

The axillary, inguinal, post-auricular, and inframammary areas are considered skin folds, where one skin layer touches another. Skin fold areas have a high moisture level and elevated temperature, both of which increase the possibility of microorganism overgrowth. A massive amount of bacteria live on the surface of the skin. Some are purely commensal; thus, only their overgrowth can cause infections, most of which are minor. In some cases, colonization of pathogenic bacteria causes more serious infections. This contribution reviews the bacterial infections of the skin fold areas.

Baboon syndrome and toxic erythema of chemotherapy: Fold (intertriginous) dermatoses.

Three decades ago, researchers described an eruption with a very characteristic distribution pattern that was confined to the buttocks and the intertriginous and flexor areas. They gave this reaction pattern one of the most unforgettable names in dermatology, baboon syndrome (BS), due to the characteristic, bright-red, well-demarcated eruption predominantly on the buttocks and genital area, reminiscent of the red bottom of a baboon. The authors described three cases provoked by ampicillin, nickel, and mercury. They were convinced that BS represented a special form of hematogenous or systemic contact-type dermatitis, but several important papers that appeared during the past decade disagreed and suggested that BS should be distinguished from hematogenous or systemic contact-type dermatitis. A new acronym, SDRIFE (symmetrical drug-related intertriginous and flexoral exanthema), was proposed along with five diagnostic criteria: (1) exposure to a systemically administered drug at the time of first or repeated doses (contact allergens excluded), (2) sharply demarcated erythema of the gluteal/perianal area and/or V-shaped erythema of the inguinal/perigenital area, (3) involvement of at least one other intertriginous/flexural fold, (4) symmetry of affected areas, and (5) absence of systemic symptoms and signs. Although there are merits to the arguments in favor of SDRIFE, many of us still prefer to use the wittier name baboon syndrome, and even more authors use both terms. We confess that we find it difficult to relinquish the term BS, which has served us so well for years; however, recognition, familiarity, and knowledge of the characteristics of this form of drug eruption must supersede sentimental attachment to a certain nomenclature and so, however reluctantly, we must embrace change. Another intertriginous drug eruption is the one induced by chemotherapy. Toxic erythema of chemotherapy (TEC) is a useful clinical term that recently has been introduced to describe this group of chemotherapy-induced eruptions. This group of overlapping toxic reactions is characterized by areas of painful erythema often accompanied by edema usually involving the hands and feet, intertriginous zones (eg, axilla, groin), and, less often, the elbows, knees, and ears. Toxic erythema of chemotherapy is briefly discussed.

Diaper (napkin) dermatitis: A fold (intertriginous) dermatosis.

Diaper (napkin) dermatitis is an acutely presenting inflammatory irritant contact dermatitis of the diaper region. It is one of the most common dermatologic diseases in infants and children. In the past, the disease was thought to be caused by ammonia; however, a number of factors, such as friction, wetness, inappropriate skin care, microorganisms, antibiotics, and nutritional defects, are important. Diaper dermatitis commonly affects the lower parts of the abdomen, thighs, and diaper area. Involvement of skin fold regions is typical with diaper dermatitis. At the early stages of the disease, only dryness is observed in the affected area. At later stages, erythematous maceration and edema can be seen. Secondary candidal and bacterial infections can complicate the dermatitis. In the differential diagnosis of the disease, allergic contact dermatitis, intertrigo, psoriasis, atopic and seborrheic dermatitis, and the other diseases should be considered. Causes of the disease should be determined and eliminated primarily. Families need to be informed about the importance of a clean, dry diaper area and the frequency of diaper changes. The use of superabsorbent disposable diapers has decreased the incidence of the disease. Soap and alcohol-containing products should be avoided in cleaning the area. In some cases, corticosteroids and antifungal agents can be administered. If necessary, antibacterial agents and calcineurin inhibitors can also be beneficial.