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RNA editing processes are strikingly different in animals and plants. Up to thousands of specific cytidines are converted into uridines in plant chloroplasts and mitochondria whereas up to millions of adenosines are converted into inosines in animal nucleo-cytosolic RNAs. It is unknown whether these two different RNA editing machineries are mutually incompatible. RNA-binding pentatricopeptide repeat (PPR) proteins are the key factors of plant organelle cytidine-to-uridine RNA editing. The complete absence of PPR mediated editing of cytosolic RNAs might be due to a yet unknown barrier that prevents its activity in the cytosol. Here, we transferred two plant mitochondrial PPR-type editing factors into human cell lines to explore whether they could operate in the nucleo-cytosolic environment. PPR56 and PPR65 not only faithfully edited their native, co-transcribed targets but also different sets of off-targets in the human background transcriptome. More than 900 of such off-targets with editing efficiencies up to 91%, largely explained by known PPR-RNA binding properties, were identified for PPR56. Engineering two crucial amino acid positions in its PPR array led to predictable shifts in target recognition. We conclude that plant PPR editing factors can operate in the entirely different genetic environment of the human nucleo-cytosol and can be intentionally re-engineered towards new targets.

Upon loss of either its chloroplast or mitochondrial target, a uniquely dual-targeted factor for C-to-U RNA editing in angiosperms reveals low evidence for improved molecular adaptation to its remaining target. RNA-binding pentatricopeptide repeat (PPR) proteins specifically recognize target sites for C-to-U RNA editing in the transcriptomes of plant chloroplasts and mitochondria. Among more than 80 PPR-type editing factors that have meantime been characterized, AEF1 (or MPR25) is a special case given its dual targeting to both organelles and addressing an essential mitochondrial (nad5eU1580SL) and an essential chloroplast (atpFeU92SL) RNA editing site in parallel in Arabidopsis. Here, we explored the angiosperm-wide conservation of AEF1 and its two organelle targets. Despite numerous independent losses of the chloroplast editing site by C-to-T conversion and at least four such conversions at the mitochondrial target site in other taxa, AEF1 remains consistently conserved in more than 120 sampled angiosperm genomes. Not a single case of simultaneous loss of the chloroplast and mitochondrial editing target or of AEF1 disintegration or loss could be identified, contrasting previous findings for editing factors targeted to only one organelle. Like in most RNA editing factors, the PPR array of AEF1 reveals potential for conceptually "improved fits" to its targets according to the current PPR-RNA binding code. Surprisingly, we observe only minor evidence for adaptation to the mitochondrial target also after deep losses of the chloroplast target among Asterales, Caryophyllales and Poales or, vice versa, for the remaining chloroplast target after a deep loss of the mitochondrial target among Malvales. The evolutionary observations support the notion that PPR-RNA mismatches may be essential for proper function of editing factors.

Summary Background Skin appearance is badly affected when exposed to solar UV rays, which encourage physiological and structural cutaneous alterations that eventually lead to skin photo-damage. Aims To test the capability of two facial preparations, extreme day cream (EXD) and extreme night treatment (EXN), containing a unique complex of Dead Sea water and three Himalayan extracts, to antagonize biological effects induced by photo-damage. Methods Pieces of organ cultures of human skin were used as a model to assess the biological effects of UVB irradiation and the protective effect of topical application of two Extreme preparations. Skin pieces were analyzed for mitochondrial activity by MTT assay, for apoptosis by caspase 3 assay, and for cytokine secretion by solid phase ELISA. Human subjects were tested to evaluate the effect of Extreme preparations on skin wrinkle depth using PRIMOS and skin hydration by a corneometer. Results UVB irradiation induced cell apoptosis in the epidermis of skin organ cultures and increased their pro-inflammatory cytokine, tumor necrosis α (TNFα) secretion. Topical applications of both preparations significantly attenuated all these effects. Furthermore, in human subjects, a reduction in wrinkle depth and an elevation in the intense skin moisture were observed. Conclusions The observations clearly show that EXD and EXN preparations have protective anti-apoptotic and anti-inflammatory properties that can attenuate biological effects of skin photo-damage. Topical application of the preparations improves skin appearance by reducing its wrinkles depth and increasing its moisturizing impact.

Background An increasing number of cutaneous adverse effects are being reported as use of statins becomes more widespread. A study was undertaken to establish the relationship between statin and a cutaneous reaction by the in vitro interferon-γ (INF-γ) release test. Methods The lymphocytes of 20 patients with suspected drug-induced skin reaction were incubated with and without the drug. The level of INF-γ from the supernatant was measured by enzyme-linked immunosorbent assay (ELISA), and the increase calculated. Results Response was positive in 27 (21.43%) of the 126 drugs. Statin was the only drug with a positive response in 80% of those cases. Nine of 20 patients (45.0%) had complete resolution after discontinuation of the drug; 6 (30.0%) who replaced one drug by another statin had partial or no resolution; and 5 (20.0%) had no resolution despite cessation of statins of all kinds. Conclusion A positive INF-γ release test was found in patients who developed skin reactions while taking statins; the test’s reliability was strengthened by prompt improvement following elimination of the suspected drug in the majority of patients.

Background. Reports have appeared that sera of patients with systemic autoimmune disorders have demonstrated autoantibodies to vinculin. Objective. To determine the presence and distribution of vinculin in the skin of patients with cutaneous autoimmune disorders. Methods. Semiquantitative immunohistochemistry investigations for presence of vinculin were conducted on skin biopsy specimens from patients with pemphigus vulgaris (PV), bullous pemphigoid (BP), and various collagen vascular diseases, and from healthy controls. Results. Results of staining for vinculin were positive in 2 of 7 PV patients, 6 of 9 BP patients, and all 6 cutaneous autoimmune patients. Staining results were negative in all controls. Strong immunostaining to vinculin was found in 3 of 6 vinculin-positive BP patients and 5 of 6 vinculin-positive cutaneous autoimmune patients. Conclusions. The expression and distribution of vinculin are accentuated in patients with various skin autoimmune diseases and appear to be stronger in diseases involving the basement membrane, where it is thought to be relatively more important than in other skin disorders.

We describe the first case of unilateral spiny hyperkeratosis (SH) of the left hand, review the literature and discuss possible patho- mechanisms. SH can be sporadic or familial, often appearing in healthy individuals. However, there is an association with various malignancies in a significant number of the sporadic cases. Although there is no satisfactory explanation of this association, we agree with previous authors that a patient with SH appearing in adult life should be evaluated and followed for the presence of malignancy. Other patients with SH may suffer from a variety of nonmalignant diseases, which may be coincidental or causally related. SH is not a premalignant lesion of the skin and should not be confused with porokeratosis which has a malignant potential. Except for excision of individual lesions, there is no permanent cure.

Background The observation of combinations of cutaneous signs that appear to be specific to autistic patients indicates a possible genetic association between autism and certain cutaneous manifestations. Objective To examine the possibility of a genetic association between autism and cutaneous manifestations in an autistic population compared to a control group of psychiatric patients. Subjects and methods Seventy-four autistic and 67 psychiatric hospitalized patients underwent routine skin examination by a physician who was unaware of the patient individual diagnosis, medical history and family background. Data on concomitant diseases, family medical history, drug therapy and dermatologic findings were compared in the two populations. Results The autistic population had a significantly higher frequency of seborrhea, atypical nevi, pigmentation, baldness and seizures, which may have a genetic background. Conclusions The findings point to the possible genetic nature of autism, a speculation that requires further study.

Objective To elucidate the relationship between the endogenous and exogenous factors involved in pemphigus vulgaris. Background Based on the observation that patients suffering hypersensitivity to penicillin often develop intercellular antibodies indistinguishable from those typical of pemphigus, it was decided to examine the hypersensitivity to a widely used semi-synthetic penicillin, ampicillin, in pemphigus vulgaris (PV) patients and their blood relatives. Methods Hypersensitivity was tested by macrophage migration inhibition factor (MIF) and mast cell degranulation (MCD) tests in 13 pemphigus vulgaris (PV) patients and 24 of their first-degree relatives. Results The humoral immune response to ampicillin was increased in PV patients and their relatives compared to controls. The cell mediated immune response was increased in the relatives compared to the controls, and negative in all patients, probably due to steroid therapy. Conclusions Increased humoral hypersensitivity to ampicillin in both PV patients and their relatives emphasizes the close relationship between drugs and the pathogenesis of the disease, and points to a possible genetic predisposition.

Background: With the introduction of systemic steroids to control pemphigus vulgaris the prognosis and survival of these patients has changed dramatically. However, in contrast to their beneficial effects, in a once almost inevitably fatal disease, the steroid therapy has created other problems, including cases of mortality. Objective: To analyze the possible factors influencing the course and prognosis of the disease and to review the steroid complications in our patients. Methods: 53 patients with pemphigus, admitted to the Department of Dermatology of Ichilov Hospital between 1965 and 1989, were studied. Results: The total mortality rate of 26.4% (14 patients of 53) in the present study is within the range found by others. A long pretreatment period did not lead to a worse prognosis. Patients with a pretreatment period longer than 6 months had a lower mortality rate than patients with a pretreatment period shorter than 6 months. The age of the patient played a role in determining the outcome of the disease as patients older than 60 years had a worse prognosis compared with patients younger than 50 years, 37.5% of the patients over 60 years died, as compared with a mortality rate of zero in patients younger than 50. This is in accordance with data found by others. Adjuvant therapy with azathioprine was found to improve the prognosis. Patients receiving azathioprine in addition to steroids had a significantly lower mortality rate and fewer exacerbations. Patients with involvement of the mucosa alone had a higher mortality rate than patients with involvement of the skin only and those with involvement of both skin and mucosa had the highest mortality rate. Conclusions: Early treatment of pemphigus does not improve the prognosis. Therefore, immediate high-dose treatment in every case of pemphigus doesn't seem absolutely essential any more.

The pathogenesis of pemphigus vulgaris (PV) is a highly controversial, "hot" topic that has received considerable enrichment in recent years by both clinical and basic researchers. On the one hand, the classical view of desmogleins (Dsg) as main targets of this autoimmune disease is supported by the characterization of pathogenic anti-Dsg3 antibodies from both patients and animal models. On the other hand, fundamental doubt has been raised towards this monopathogenic view by several independent factors: (1) pemphigus lesions can be induced in Dsg3-knockout (KO) mice; (2) pemphigus sera contain multiple autoantibodies against different adhesion molecules and also cholinergic receptors; (3) experimental inhibition of PV IgG induced acantholysis can be obtained by interference with different signaling cascades regulating both calcium homeostasis and apoptosis; and (4) cholinergic agonists exhibit anti-acantholytic activity both in vitro and in vivo. The field is open for controlled clinical trials and further basic research to unfold the true story of the pemphigus enigma and provide the basis for a better treatment of pemphigus patients.

Pemphigus vulgaris (PV) is a human leukocute antigen (HLA) class II-associated autoimmune disease of the skin of unknown etiology. We recently described the association of pemphigus vulgaris with two clusters of microsatellite loci within the major histocompatibility complex region. One cluster includes the microsatellite marker TAP1CA, located in proximity to the transporter associated with antigen processing (TAP) genes. These genes are essential for class I antigen processing machinery and could be an additional set of genes involved in susceptibility to PV. The aim of this study was to investigate a possible association between TAP gene polymorphisms and PV. For this purpose we examined 37 unrelated Jewish Israeli patients with PV and compared them with 37 healthy Israeli Jewish HLA-matched controls. Significant differences were detected in TAP2 amino acid residues (p = 0.001). Two PV TAP2 risk alleles were identified (TAP2*C and TAP2*D), the frequency of which was estimated to be 37.8% in the patients and 5.3 % in the controls. This association was found to be independent of HLA-DR. It is therefore likely that TAP2 genes are involved in susceptibility to development of PV.

Here's a helpful review of what goes right and what can go wrong in the female and male breast, with emphasis on dermatologic and developmental disorders. New issues are demanding the clinician's attention, including the cosmetic effects of nipple piercing and tattooing.

A 54-year-old man of Persian origin presented to our department with a 1-year history of ulcers on the right leg that had been unresponsive to numerous topical treatments, accompanied by lymphedema of the right leg. Medical history included hypergonadotropic hypogonadism, which had not been further investigated. He was treated for 20 years with testosterone IM once monthly, which he stopped a year before the current hospitalization for unclear reasons. The patient reported no congenital lymphedema. Physical examination revealed two deep skin ulcers (Figure 1) on the right leg measuring 10 cm in diameter with raised irregular inflammatory borders and a boggy, necrotic base discharging a purulent hemorrhagic exudate. Bilateral leg pitting edema and right lymphangitis with lymphadenitis were noted. He had low head hair implantment, sparse hair on the body and head, hyperpigmentation on both legs, onychodystrophia of the toenails (mainly the large toe and less prominent on the other toes), which was atrophic lichen-planus-like in appearance and needed no trimming (Figure 2), normal hand nails, oral thrush, and angular cheilitis. Other physical findings were gynecomastia, pectus excavatum, small and firm testicles, long extremities, asymmetrical goiter, systolic murmur 2/6 in left sternal border, and slow and inappropriate behavior. The patient's temperature on admission was 39 degrees C. Blood cultures were negative for bacterial growth. Results of laboratory investigations included hemoglobin (11.2 g/dL), hematocrit (26.8%), normal mean corpuscular volume and mean corpuscular hemoglobin volume, and red blood cell distribution width (16%). Blood smear showed spherocytes, slight hypochromia, anisocytosis, macrocytosis, and microcytosis. Blood chemistry values were taken for iron (4 micro g/dL [normal range 40-150 micro g/dL]), transferrin (193 mg/dL [normal range 220-400 mg/dL]), ferritin (1128 ng/mL [normal range 14-160 ng/mL]), transferrin saturation (1.5% [normal range 20%-55%]), serum folate (within normal limits), and vitamin B12 (within normal limits). Direct Coombs' test equaled positive 2 + IgG. All these values indicated anemia of chronic diseases combined with hemolytic anemia. Further blood work-up tested antinuclear antibody (positive1:80 homogeneous pattern), rheumatoid factors (143 IU/mL [positive8.5 IU/mL]), C-reactive protein (286 mg/L [normal range 0-5 mg/L]), anticardiolipin IgM antibody (9.0 monophosphoryl lipid U/mL [normal range 0-7.00 MPL U/mL]) and antithrombin III activity (135% [normal range 74%-114%]). Results of other blood tests were within normal limits or negative, including lupus anticoagulant, beta2 glycoprotein, anticardiolipin IgG Ab, anti-ss DNA Ab, C3, C4, anti-RO, anti-LA, anti-SC-70, anti-SM Ab, P-ANCA, C-ANCA, TSH, FT4, anti-T microsomal, antithyroglobulin, protein C activity, protein S free, cryoglobulins, serum immunoelectrophoresis, VDRL, hepatitis C antibodies, hepatitis B antigen, and human immunodeficiency virus. Endocrinological work-up examined luteinizing hormone (22.9 mIU/mL [normal range for adult men 0.8-6 mIU/mL]), follicle stimulating hormone (49.7 mIU/mL [normal range for adult men 1-11 mIU/mL]), testosterone (0.24 ng/mL [normal range for adult men 2.5-8.0 ng/mL]), bioavailable testosterone (0.02 ng/mL [normal range for adult men0.6 ng/mL]), and percent bioavailable test (8.1% [normal value20%]). These results indicate hypergonadotropic hypogonadism. Plasminogen activator inhibitor 1 was 6 U (normal value 5-20 U/mL). Karyotyping performed by G-banding technique revealed a 47 XXY karyotype, which is diagnostic of Klinefelter's syndrome. Doppler ultrasound of the leg ulcers disclosed partial thrombus in the distal right femoral vein. X-rays and bone scan displayed osteomyelitis along the right tibia. Histological examination of a 4-mm punch biopsy from the ulcer border revealed hyperkeratosis, acanthosis, hypergranulosis, and mixed inflammatory infiltrate containing eosinophils compatible with chronic ulcer. Multiple vessels were seen, compatible with a healing process. Direct immunofluorescence of the biopsy revealed granular IgM in the dermo-epidermal junction. Indirect immunofluorescence was negative. Thyroid function tests showed normal thyroid stimulating hormone and free throxine4. Multinodular goiter was seen on thyroid scan and ultrasound. Thyroid fine needle aspiration was compatible with multinodular goiter (normal follicular cells, free colloid, macrophages with pigment). IV treatment with amoxicillin-clavulanic acid 1 g t.i.d. was administered for 2 weeks, with a decrease in temperature and normalization of the leukocyte level. Oral antibiotic treatment with amoxicillin-clavulanic acid was continued for 10 more days, followed by 25 days of ciprofloxacin for the osteomyelitis. Local treatment included saline soakings followed by application of Promogran (JohnsonJohnson, New Brunswick, NJ) and Kaltostat (ConvaTec Ltd., a Bristol-Myers Squibb Company, New York, NY) with slight improvement. At the same time, the patient was treated with warfarin sodium due to deep vein thrombosis under international normalized ratio 2-3. The patient was treated with IM testosterone once monthly for 1 year, which resulted in a reduction in the diameter and depth of the leg ulcers (Figure 3). Blood tests were not performed for follow-up of the immune state.

Hirsutism, the appearance of facial hair on women in a male pattern distribution, is a problem with potential medical, social, and psychological implications for millions of women. Hirsutism can reflect the presence of an underlying systemic disease, namely one that results in hyperandrogenic states, or it may seem to be idiopathic. Many methods of treatment have been used over the years, from pharmacological and surgical treatment for underlying disease to mechanical means of hair removal. We discuss hirsutism and review the clinical experience with a topical cream approved for facial hair removal, called eflornithine (Vaniqa), which acts by inhibiting new growth by an enzyme inhibition mechanism. Therapeutic trials and our clinical experience have shown promising results with this agent in diminishing unwanted facial hair in women.

Pemphigus is a group of autoimmune blistering diseases of the skin and mucous membranes. The association of pemphigus with human leukocyte antigen (HLA) is widely accepted. It was described in many ethnic groups and in most countries of the world. Studies showed that the associated HLA haplotype in Jewish pemphigus vulgaris (PV) patients is HLA-B38, DRB1*0402, and DQB1*0302; or HLA-B35, DRB1*0402, and DQB1*0302. Similar associations with class II genes were found in Spanish non-Jewish PV patients. As Jews lived in Spain for hundreds of years and many converted to Christianity, the presence of the same HLA haplotype in the Jewish and Spanish PV suggests that they may share the same founder. Microsatellite markers which span the entire major histocompatibility complex (MHC) locus were used as genetic probes. They were utilized to dissect the MHC region in the search for possible common haplotypes, besides HLA, which may provide an answer to this question. It was found that in both cohorts, in addition to HLA class II genes, there are probably genes in the class I region which are associated with PV. Alleles belonging to the associated markers were used to construct haplotypes and to estimate genetic distances. The distance between the two PV cohorts is relatively short, but the distance between the Jewish patients and the Jewish controls is greater compared to the distance between Spanish patients and Spanish controls. In both PV populations, the same microsatellite haplotypes in addition to a common class II haplotype were found, suggesting that both patient populations originated from the same genetic stock and, therefore, share the same ancestral disease gene.

Male gender is interpreted as a risk factor for developing mycosis fungoides and perhaps other cutaneous and extracutaneous lymphomas. In this review the authors examine epidemiologic, clinical, pathologic, and molecular data in an effort to understand whether and to what extent gender or sex hormones are involved in the pathogenesis of lymphoproliferative disorders.

Pemphigus is an autoimmune bullous disease that may be influenced by genetic and exogenous factors. Drugs are a leading cause of pemphigus. There is a need for a thorough history taking so as to find the culprit medication. The diagnosis of drug-induced pemphigus is challenging. Patients have often been exposed to multiple drugs, and some drugs may have a prolonged latency period between exposure and onset of the disease. The in vitro interferon-gamma (IFN-gamma) release from lymphocytes test has been shown to be of diagnostic value in drug-induced skin reactions. Cessation of the offending drug may alleviate the clinical manifestations and reduce the need for medical treatment.

A patient with severe ichthyosiform erythroderma and lichenoid histological changes is presented. We discuss the clinical and histological differential diagnosis, including lupus erythematosus, lichenoid drug eruption, lichen planus, graft-versus-host disease, lymphoma, keratosis lichenoides chronica, Netherton's syndrome and ichthyosiform erythroderma. None of these is consistent with the features in our case, which may represent either a hitherto unreported form of ichthyosiform erythroderma or possibly a new entity.

Similar lesion topography which resembled an inverted fir tree in two patients with nifedipine-related pemphigus vulgaris is described. The possible relation of the lesion pattern to the offending drug is discussed.

Background An increase in the incidence of cutaneous malignant melanoma in recent years has not been accompanied by satisfactory progress in diagnostic methods. This study was carried out to evaluate a specially designed computerized image analysis system, called Derma Vision, to aid in the differentiation between malignant and benign cutaneous pigmented lesions. Methods Seventy-one lesions were photographed with a digital camera and the data were analyzed by the Derma Vision system. The system assessed the variation of hues in each image, calculated the mean standard deviation of the hues, and produced a value that expressed the range of hues in the lesion. The lesions were then excised and examined histologically. The computer-assisted clinical diagnosis was correlated with the histologic diagnosis to determine the accuracy of the former. Results Derma Vision predicted the malignant character of a lesion with 92% precision, compared with 87% accuracy based only on the clinical features. Conclusions This simple, inexpensive device can boost the accuracy of clinical diagnosis and provide a useful tool to the physician faced increasingly with having to determine whether pigmented lesions are malignant or benign.

We describe the case of a woman with the classic combination of features of synovitis-acne-pustulosis-hyperostosis-osteitis (SAPHO) syndrome, including pustulosis palmo-plantaris and anterior chest wall involvement. The varying symptomology, etiology and pathogenesis of this syndrome and the contribution of stress are discussed. The authors ascribe the dearth of reported cases to lack of awareness and recognition of SAPHO, and not to the real incidence of the syndrome.

Background A variety of drugs have been implicated in the onset and exacerbation of pemphigus and bullous pemphigoid. The demonstration of biochemical acantholysis in skin explants to various drugs in the absence of autoantibodies, in which the tested drugs evoke a biochemical reaction that leads to desmosomal function loss, may be a valuable adjunct to patient management by confirming the suspicion of drug-related pemphigus or bullous pemphigoid. Objective To determine whether a skin explant model might serve as a possible in vitro correlate of drug-induced pemphigus and pemphigoid-like effects related to the calcium channel blocker nifedipine. Methods Normal human breast skin obtained from nonpemphigus and nonpemphigoid patients undergoing mastectomy was cultured with nifedipine at final concentrations of 2, 4, and 8 mm. The drug effect on skin explants evidenced by morphologic changes was evaluated by microscopy by three observers. Results Five out of seven explants cultured with nifedipine at concentrations ranging from 2 to 8 mm exhibited obvious morphologic changes of two types: intraepithelial (or pemphigus-type) splittings and subepithelial (or pemphigoid-type) splittings. Two explants showed no acantholysis and no subepithelial splittings. Control cultures without polyethylene glycol 200 (PEG) showed no changes. Skin control samples cultured in medium supplemented with 10% PEG displayed vacuolar degeneration throughout the entire epidermis, but no sign of cell–cell dyshesion or dermo-epidermal detachment. Conclusions A type of skin susceptibility to nifedipine may be genetically determined, with some nifedipine-treated patients developing an acantholytic reaction and others a subepidermal bullous eruption.

An 82-year-old healthy woman presented with bullae, partly hemorrhagic, on the trunk and extremities (Fig. 1), secreting erosions, and submammary macerations (Fig. 2). The blistering disease developed over a 2-year period, during which she reported taking no drugs. She did, however, begin using a food supplement containing the blue–green alga Spirulina platensis 1 year before the onset of the eruption. Figure 1. Hemorrhagic bullae on the extremities Download figure to PowerPoint Figure 2. Submammary bullae, secreting erosions, and macerations Download figure to PowerPoint At admission, the Nikolsky sign was positive. The first biopsy showed a subepidermal bulla with a denuded surface and sparse perivascular lymphocytic infiltrate with scattered eosinophils (Fig. 3). The second biopsy, taken during admission, demonstrated an intra- and subcorneal vesicular dermatitis with slight superficial acantholysis. Direct immunofluorescence disclosed immunoglobulin G (IgG) and C3 at the dermoepidermal junction. Indirect immunofluorescence was also positive at the dermoepidermal junction. A salt split test demonstrated IgG, IgM, and C3 on the upper side of the bulla. Immunoblotting of the serum was negative and showed no pemphigoid or pemphigus antigens. Enzyme-linked immunosorbent assay (ELISA) for desmoglein 1 and 3 antibodies was also negative. Figure 3. The first biopsy showing subepidermal hemorrhagic bulla with denuded surface and sparse perivascular lymphocytic infiltrate with scattered eosinophils (hematoxylin and eosin, ×10) Download figure to PowerPoint Diagnostic investigations for neoplasia, Wood's lamp exposure of urine, purified protein derivative (PPD), and antinuclear antibody (ANA) were negative. With a diagnosis of mixed immunoblistering disorder exhibiting features of bullous pemphigoid and pemphigus foliaceus, prednisone 60 mg was started and gradually tapered, and topical treatment was begun with creams containing silver sulfadiazine and triamcinolone/neomycin. Suspecting the involvement of Spirulina in the disease, the food supplement was stopped. With this treatment, the patient steadily improved with no appearance of new blisters. An in vitro interferon-γ release test with the Spirulina-containing food supplement, conducted to explore the connection between the agent and the eruption, yielded a slight increase in interferon (19%). The result was considered to be borderline, but, in view of the clinical picture and the fact that the patient was being treated with 20 mg prednisone at the time, the test can be considered as positive. Three months after completion of the prednisone treatment, and with avoidance of the Spirulina-containing supplement, the patient was free of lesions with no recurrences.

Sarah Brenner† & Yonit Wohl †Author for correspondence Tel Aviv University, Department of Dermatology, Tel Aviv-Sourasky Medical Center, 6 Weizmann Street, Tel Aviv 64239, Israel Tel.: +972 3697 3356; Fax: +972 3697 4810; E-mail: derma@ tasmc.health.gov.il ‘The coining of the term ‘gender dermatology’ heralds a shift in focus from research directed mainly at women’s health to a more comprehensive approach to the biological features of health and illness in each gender.’

Palmoplantar eccrine hidradenitis (PEH) is characterized by painful erythematous papules and nodules of abrupt onset on the soles of young individuals. The histologic hallmark is a predominant neutrophilic infiltrate surrounding the eccrine gland apparatus. A total of 28 cases have been published since 1988, with a broad variation in the age of patients, symptomatology, associated diseases, clinical course, and histologic features. These different histologic pictures have resulted in several names for this entity, including idiopathic plantar hidradenitis, neutrophilic eccrine hidradenitis, recurrent palmoplantar hidradenitis in children, and idiopathic palmoplantar hidradenitis. We present three cases of this disorder and review the literature on the varying symptomatology, clinical course, and histology that have led to the myriad of names for this disease.

Dorfman-Chanarin syndrome, or neutral lipid storage disease with ichthyosis, is a rare inherited metabolic disorder characterized by accumulation of neutral lipids in different tissues. Variability in dermatologic severity is not understood. We report two new cases, compare their features with other reported cases, and examine the possible relationship between the severity of the dermatologic condition and lipid accumulation in various types of skin cells. The localization of lipid droplets was determined in various dermal and epidermal cells by light microscopy of epoxy resin semithin sections and electron microscopy in four cases of Dorfman-Chanarin syndrome. Lipid droplets in the dermis were detected in fibroblasts, Schwann cells in both myelinated and unmyelinated nerves, smooth muscle cells, and sweat gland cells, but not in endothelial cells of blood capillaries. The droplets were not surrounded by a membrane. Findings indicate that there is no correlation between the clinical severity of the disease and the microscopic findings.

Background Histamine is considered a major mediator in the process of gastric acid secretion. When acid peptic activity overpowers the mucosal defense mechanism, peptic ulceration may develop. Is the hyperreactivity of patients with duodenal ulcer to histamine also expressed in the skin? Objective The aim of the present study was to assess the reactivity of patients with duodenal ulcer to histamine as reflected in the skin, by comparing the erythema and the cutaneous blood flow response to histamine in duodenal ulcer patients and healthy controls. Methods Twenty volunteers participated in the study: 10 duodenal ulcer patients and 10 age and gender matched healthy controls. Histamine was topically administered to the back and to the volar side of the forearm, and the induced response was quantified by spectrophotometry and laser Doppler flowmetry (LDF). The extent of the response and time parameters were compared. Results The maximum response, as measured by LDF, was greater in the peptic ulcer patients (P

Background: Twelve cases of contact dermatitis provoked by Agave americana are described, 10 with systemic signs and symptoms and 8 with abnormal laboratory results. Results: Patient history revealed a background of intentional exposure among soldiers seeking sick leave. Treatment with oral antihistamines and topical saline compresses resulted in subsidence of the systemic symptoms within 24 h of hospitalization and regression of cutaneous manifestations in 7–10 days. Conclusion: The importance that dermatologists be alert to the possibility of self-inflicted contact dermatitis induced by exposure to plants is stressed, especially to A. americana. Systemic signs are not rare accompanying findings with this plant.

A 41-year-old woman presented with a 2-month history of pruritus and a generalized dermatitis that developed initially on the head and spread to the trunk, legs, and buttocks. The pruritus caused extreme discomfort and was not relieved by antihistamines or topical steroid treatment. The patient denied flushing, syncope, and vomiting. Her medical history included asthma treated with salmeterol/fluticasone propionate inhaler, and status post silicone breast augmentation. Physical examination revealed a papular dermatitis on the trunk and extremities composed of lesions up to 0.5 cm in diameter, surrounded by excoriation marks (Figure 1). There was no hepatosplenomegaly or lymphadenopathy. Darier's sign was negative. Results of complete blood count, peripheral blood film examination, and liver function tests were all with normal limits. A biopsy specimen taken from a lesion and stained with hematoxylin-eosin showed telangiectasias, with an increased number of mast cells around blood vessels (Figure 2). Positive Giemsa (Figure 3) and c-kit stain (Figure 4) indicated an increased number of mast cells. Bone marrow aspiration and total body CT performed to rule out systemic involvement showed no pathology. Protein electrophoresis was normal. Serum tryptase and histamine were within normal limits, and 24-hour urine collection for histamine was normal. Narrow-band UV-B treatment was begun 3 times weekly, reduced to twice weekly after 2 months, and then stopped. The first few treatments resulted in significant relief of the pruritus and regression of lesions. After 3 months without treatment, the patient remained free of pruritus and lesions.

Contact dermatitis is one of the leading causes of occupational morbidity and absenteeism and has become an intolerable cause of missed workdays and health problems in the Israeli military. The aim of this study was to determine the rate of contact dermatitis in maintenance and clerical workers, the common allergens causing it, and the background of atopy in the subjects in order to design preventive measures. Medical records of all recruits to the Israel Defense Forces from 2000 to 2003 were reviewed for contact dermatitis. The 102 cases found were further assessed for job assignment, atopic background, and allergens. Of the 102 cases, 60 had irritant contact dermatitis and 42 had allergic contact dermatitis, of which 33 (78.6%) were maintenance workers, mainly mechanics. 13 soldiers in the maintenance job category (39%) and 2 soldiers in the clerical group (22.2%) had atopic background. There were 55 positive reactions in patch tests, 25 of them to oil and cooling fluids, with 14.5% attributed to methylchloroisothiazolinone/methylisothiazolinone) (Kathon CG). Atopy was found to be a risk factor for allergic contact dermatitis in our study and should be screened for in job assignment procedures in the military. Oil and greases contain significant allergens, especially their preservatives.

Pemphigus subclasses differ both in target epidermal antigen of the autoantibodies and in predilection sites of lesions. The patterns of lesions are well documented and often lead to diagnosis of the subtype of the disease; but the causative factors have never been studied. We present a case of pemphigus exacerbated by two unrelated drugs, with distinct exacerbation-specific patterns following each drug consumption. The patient is regarded as exemplifying a fixed drug eruption-like phenomenon, with specificity of drug to anatomic distribution of lesions.

Background: Patients with pemphigus vulgaris (PV) are genetically linked to two alleles of the HLA subgroup, and circulating antibodies were found in first-degree relatives of these patients, thus showing genetic predisposition. Objective: Our purpose was to determine the occurrence of circulating true PV-IgG in patients' relatives. Methods: Circulating PV-IgG was determined in 21 first-degree relatives of 12 patients with PV by indirect immunofluorescence on monkey esophagus, carcinoma A431 cultures, and Western immunoblotting. Direct immunofluorescence was performed on skin biopsy specimens of 20 relatives. Results: Circulating PV-IgG was detected in 15 relatives (71%) by all methods tested. Good correlation was found between immunoblot reactivity and immunofluorescence. Of the 15 "positive" relatives, only five showed fixation of IgG to epidermal cells in vivo. Conclusion: The permeability of the epidermis or epidermal cell reactivity in vivo probably controls the expression of disease in patients' relatives. (J Am Acad Dermatol 1997;36:44-52.)