An Update on the Cutaneous Manifestations of Darier Disease.

BACKGROUND: Knowledge about the clinical features of Darier disease, an orphan autosomal-dominant genetic disorder, is sparse and has been evaluated only in few studies. OBJECTIVES: To investigate the clinical features of a large group of patients with Darier disease, and to explore for associations between disease characteristics and severity of the disease. METHODS: Seventy-six individuals with Darier disease were evaluated utilizing a structured questionnaire-based interview, a physical examination, and a retrospective assessment of their medical records. RESULTS: The most frequent locations of lesions were hands (99%) and fingernails (93%). Wart-like lesions on the hands were more visible after soaking them in water for 5 minutes, we therefore named this phenomenon the "wet hand sign". Oral involvement was found in 43% of patients, while 48% of women and 16% of men showed genital lesions. Patients with severe Darier disease had a tenfold greater risk of developing genital lesions than those with mild disease (P = .01). Most patients (88%) in our study exhibited a combination of the four types of the disease patterns of distribution (flexural, seborrheic, nevoid, and acral). CONCLUSIONS: Documentation of disease on the hands and fingernails provides a highly sensitive means to aid in the diagnosis of Darier disease. It is important to evaluate mucosal lesions including genital and oral mucosa.

[BULLOUS PEMPHIGOID RESISTANT TO CORTICOSTEROIDS].

INTRODUCTION: Bullous pemphigoid is the most common autoimmune bullous disease, treated with low dosage local or systemic corticosteroids. This is a case report of a 65 years-old female patient with a month long history of a bullous disease before admission to the dermatology department with a generalized bullous rash. Clinical examination and histopathology revealed bullous pemphigoid. She was treated according to the established protocol with systemic corticosteroids. The amount of prednisone was raised to 100mg per day for 8 weeks without any noticeable improvement, instead there was a worsening of her symptoms. In light of the treatment failure we carried out an adrenocorticotropic stimulation hormone test with a normal result. The patient was diagnosed as being resistant to corticosteroids and the treatment with prednisone was immediately terminated. Treatment was initiated with cyclophosphamide with an immediate improvement in her symptoms, and the patient was discharged after complete recovery. Discussion: Resistance to corticosteroids is a rare occurrence that has been reported in the literature on pulmonary and gastric disease. In dermatology, there is a single case report on atopic dermatitis that was treated locally. Awareness of the possibility will allow for a prompt diagnosis and appropriate treatment. Conclusion: We presented the case of a 65 year old female with bullous pemphigoid resistant to corticosteroids that has not been previously reported in the dermatologic literature.

[CUTANEOUS T CELL LYMPHOMA: UNILESIONAL MYCOSIS FUNGOIDES].

INTRODUCTION: Unilesional mycosis fungoides is a rare cutaneous T cell lymphoma that warrants either radiation therapy or surgical excision. Benign characteristics result in misdiagnosis, delayed tissue biopsy and subsequently delayed provision of adequate treatment. A young patient presented with a history of 18 months of eczematous benign - appearing single lesion restricted to her index finger. Local electron-beam radiation following tissue diagnosis resulted in full recovery.

Combination therapy of cyclosporine and anti-tumor necrosis factor α in psoriasis: a case series of 10 patients.

Combination therapy has become important in treating psoriasis, using synergism between different mechanisms to maximize efficacy and minimize toxicity. Little has been published on the combination of cyclosporine and anti-tumor necrosis factor (TNF) α agents. In this study, a retrospective chart review was made of the effects of this combination therapy in 10 patients with recalcitrant psoriasis. Treatment included a conditioning phase with cyclosporine, 3.14 ± 0.37 mg/kg for 4.6 ± 2 weeks, and a combination phase during which etanercept/adalimumab were initiated and cyclosporine was tapered over 10.2 ± 3.7 weeks. Treatment success, evaluated after each phase, was classified as complete recovery (CR, more than 75% improvement), partial response (PR, 25-75% improvement), and no response (NR, less than 25% improvement). All patients reached CR at the end of the combination therapy. Two were still on combination therapy after 12 and 20 weeks. Adverse event occurred in three cases, all in the conditioning phase. We conclude that combination therapy with cyclosporine and anti-TNF α appears to offer an effective and safe approach to treatment of psoriasis.

[Prevalence of thyroid abnormalities among psoriatic patients].

INTRODUCTION: Psoriasis is a chronic papulosquamous cutaneous disease. The etiology is unknown. Several biochemical and immunological processes, which appear in patients with genetic predisposition, lead to enhanced proliferation of epidermal cells, and inflammation of the dermis. Thyroid gland hormones cause an increase of epidermal growth factor level, which has an important role in keratinocyte proliferation, which may be involved in psoriasis disease. METHODS: In this study, we have prospectively examined the function of thyroid gland hormones--TSH, T3, T4, anti-TPO and antithyroglobulin--in 100 psoriatic patients. This database was compared with a control group of 54 patients, without known thyroid gland abnormalities, who were randomly chosen from the endocrinology clinic's medical records. RESULTS: In the psoriatic patients, an increase in the anti-TPO levels was demonstrated in 9 psoriatic patients (9%), compared to 3 patients in the control group (5.6%). An increase of anti-TG was demonstrated in 3 psoriatic patients (3%) compared to one patient (1.8%) in the control group. An increase of TSH levels was demonstrated in 5 psoriatic patients (5%) compared to 3 patients (5.6%) in the control group. T3 levels were abnormal in 3 psoriatic patients, and T4 levels were abnormal in 2 psoriatic patients, while the T3 and T4 levels in the control group patients were normal. CONCLUSIONS: In our study we didn't observe a statistical difference in the thyroid gland functions between the psoriatic and the control patients. We have observed that in patients with severe psoriasis, there were increased TSH levels and positive auto-antibodies titer compared to patients with mild psoriasis. SUMMARY: The clinical characteristics of the psoriatic patients were connected to the function of the thyroid gland. Nonetheless, the number of patients was low, and more studies are needed to confirm this relationship.

The relationship between sensory hypersensitivity and sleep quality of children with atopic dermatitis.

This study aims to investigate the impact of sensory hypersensitivity in children with atopic dermatitis (AD) and to evaluate a possible relationship between sensory hypersensitivity, sleep quality and disease severity in AD. Fifty-seven AD patients and 37 healthy children, aged 3-10 years, participated in this study. Disease severity was assessed using the Severity Scoring of Atopic Dermatitis (SCORAD) Score. The sensory profile was assessed using the Short Sensory Profile (SSP) and sleep characteristics were evaluated using the Children's Sleep Habits Questionnaire (CSHQ). The AD group demonstrated significantly worse sleep quality compared with the controls in the following CSHQ subscales: sleep duration; parasomnias; sleep disordered breathing and daytime sleepiness. Sensory hypersensitivity was correlated with lower sleeping quality. Severity Scoring of Atopic Dermatitis Scores was positively correlated with sleep anxiety and with parasomnias. Sensory hypersensitivity and disturbed sleep patterns were common in the children with AD that participated in this study. A possible common underlying mechanism of hyper-arousability may account for both phenomena. Evaluation of AD children should also refer to their sensory processing abilities and sleep habits to create optimal intervention programs that will be better focused on the child and family needs.

Allopurinol-induced recurrent DRESS syndrome: pathophysiology and treatment.

Hyperuricemia is present in approximately 5% of the population. The vast majority is asymptomatic and at no clinical risk. Allopurinol, an analog of hypoxanthine, has been widely used in clinical practice for more than 30 years for the treatment of hyperuricemia and gout. Two percent of patients develop a mild exanthema when on this drug, which usually resolves after withdrawal of the drug. A syndrome characterized by exfoliative dermatitis, hepatitis, interstitial nephritis, and eosinophilia, termed allopurinol hypersensitivity syndrome, has been described, and its etiology related to the accumulation of one of allopurinol's metabolites, oxypurinol, of which clearance is decreased in the setting of renal insufficiency and the use of thiazide diuretics. The term DRESS (Drug Rash with Eosinophilia and Systemic Symptoms) Syndrome has been recently used to describe an entity presenting with similar features.

Profile of acute generalized exanthematous pustulosis in Israel during 2002-2005: results of the RegiSCAR Study.

BACKGROUND: Acute generalized exanthematous pustulosis is a rare pustular severe cutaneous adverse reaction characterized by a rapid clinical course and unique histological findings. It is usually attributed to drugs, although other factors have also been implicated. OBJECTIVES: To analyze demographic, clinical and laboratory data of AGEP cases in Israel, based on the RegisCAR study, a multinational European study. METHODS: Patients included in the present study were actively recruited by the Israeli RegiSCAR network, which comprised 10 dermatology departments and units. The cases were validated by a multinational expert committee of dermatologists based on a standardized scoring system. RESULTS: Overall, 11 potential cases of AGEP were collected in Israel: 9 (81.8%) definite and 2 (19.2%) possible. The adjusted annual incidence of AGEP in Israel was 0.35/million/year. The nine definite cases that entered the analyses showed a male/female ratio of 0.28 with an age range of 10-60 years. Most cases were reported during the summer months. The clinical course and laboratory findings in most of our patients were in accordance with previous reports. A drug etiology was suspected in the majority of cases and consisted of analgesics (66.7%), antibiotics (22.2%) and non-steroidal anti-inflammatory drugs (11.1%) as the main culprit drugs. CONCLUSIONS: Whereas the clinical and laboratory findings of AGEP in Israel corresponded to the reported features of AGEP in the literature, some unique findings were noted, namely, marked female predominance, seasonality and a profile of culprit drugs.

The sensory profile of children with atopic dermatitis as determined by the sensory profile questionnaire.

BACKGROUND: The increasing prevalence of atopic dermatitis (AD) combined with the limited efficacy of current therapies emphasizes the need to improve care quality for patients with AD. This study aims to characterize the sensory profile of children with AD as expressed in daily living. METHODS: In all, 53 patients with AD and 61 healthy children, aged 3 to 10 years, participated in this study. Disease severity was assessed using the Severity Scoring of AD (SCORAD) score. The sensory profile was assessed using the Short Sensory Profile. RESULTS: The study group had significantly higher sensory sensitivity than the control group (t = 2.855; P = .013). These results were seen in all sensory modalities except vestibular sensation. LIMITATIONS: This study was composed of a relatively small number of participants with a wide spectrum of disease severity. CONCLUSIONS: Children with AD demonstrated hypersensory sensitivity. Understanding the sensory and behavioral characteristics of children with AD can promote the development of innovative intervention processes better geared to focus on patients' needs.

Nontuberculous mycobacterial infections of the skin: A retrospective study of 25 cases.

BACKGROUND: Absence of a pathognomonic clinical picture and variable histologic findings often delay diagnosis of nontuberculous mycobacteria (NTM)-induced cutaneous infections, and antimicrobial therapy varies. OBJECTIVE: We sought to investigate the clinical, microbiologic, and pathological findings of cutaneous NTM infections and response to different treatments. METHODS: Records of patients with NTM infections of the skin confirmed by positive cultures or histologic findings were reviewed. Clinical, microbiologic, and epidemiologic data were collected and skin biopsy specimens were reassessed. RESULTS: The series included 25 cases, one diagnosed by histology and 24 by positive culture: 16 cases with Mycobacterium marinum, 3 of atypical Mycobacterium without species identification, and one each with M chelonae, M xenopi, M abscessus, M gordonae, and M fortuitum. One of 16 patients with M marinum developed tenosynovitis. Mean interval between clinical presentation and diagnosis was 7.1 months (range: 1-27.3 months). All isolates analyzed for antimicrobial susceptibility pattern were sensitive to clarithromycin. LIMITATIONS: Limitations include methods of case collection, retrospective study, and relatively small number of patients. CONCLUSIONS: Diagnosis of NTM should be confirmed by histology and bacteriology studies of tissue cultures. Strong clinical suggestion of M marinum infection warrants initial empirical treatment to prevent progression to deep infection. The recommended treatment as indicated by the results of the in vitro susceptibility and clinical response is clarithromycin.

Acute generalized exanthematous pustulosis following a spider bite: report of 3 cases.

Acute generalized exanthematous pustulosis (AGEP) is a rare severe cutaneous adverse reaction caused mostly by drugs. Three of 22 AGEP cases (13.6%), recruited by us as part of two prospective multinational studies, occurred 24 to 48 hours after a spider bite. We suggest that a spider bite is a possible trigger for AGEP.

Unusual skin and testicular lesions in a patient with CMML.

Chronic myelomonocytic leukemia (CMML) is a clonal disorder of hematopoetic stem cells with myelodysplastic and myeloproliferative features. Skin infiltration by leukemic cells is rare in CMML. A case is presented with severe dermatological involvement and concomitant testicular infiltration. An unusual feature was the evidence that the skin was the primary site of an acute leukemic transformation.

Sister Mary Joseph's nodule as a presenting sign of internal malignancy.

CASE 1: A 64-year-old, otherwise healthy woman was referred to the surgery clinic for a presumed umbilical hernia. On physical examination, a cutaneous nodule was noted on the umbilical region and the patient was referred to the dermatology clinic. The patient was reexamined and an erythematous nodule was observed in the umbilicus measuring 2.5 cm in diameter. The patient denied pain, change in bowel habits, or weight loss. There were no other abdominal masses, no sign of ascites, and no regional lymphadenopathy. A skin biopsy from the nodule showed mucinous adenocarcinoma. Immunohistochemical staining was positive for carcinoembryonic antigen, and negative for cytokeratin (CK)7 and CK20. These results were consistent with a Sister Mary Joseph's nodule and led to the diagnosis of an occult colon carcinoma. The patient had no risk factors for colorectal carcinoma. The patient underwent surgery in another hospital, and died 3 months after the initial diagnosis of Sister Mary Joseph's nodule. CASE 2: A 73-year-old woman was referred to the dermatology clinic for evaluation of a painful, ulcerated, 3-cm lesion in the umbilicus (Figure 1). She was otherwise asymptomatic. A skin biopsy showed neoplastic glandular cells infiltrating among collagen bundles (Figure 2). Stainings for mucin and for CK7 were positive, while staining for CK20 was negative. An abdominopelvic CT scan demonstrated a 3.5-cm space-occupying lesion in the liver. Results of gastroscopy, colonoscopy, chest computed tomographic (CT) scan, and mammography were normal. Serum levels of the tumor-associated protein CA125 were elevated to 164 units, while those of CA 19-9 and carcinoembryonic antigen were within normal range. A gynecologic examination and a transvaginal ultrasound were normal. The patient had no personal or family history of any malignancy or any risk factors for developing a carcinoma. The patient was scheduled for a palliative resection of the umbilical nodule, combined with a laparoscopic inspection in search of the undetected primary tumor. She refused surgery and was lost to follow-up. She died 4 months after the initial diagnosis of umbilical metastasis. CASE 3: A 51-year-old man was aware of a silent mass in his umbilicus for 2 years without seeking medical advice. Following 2 weeks of increasing pain in this area, he was referred to the emergency room for a suspected incarcerated umbilical hernia. Surgery revealed a mass attached to the fascia and peritoneal fat. The mass was removed and diagnosed as a poorly differentiated adenocarcinoma, staining positively for carcinoembryonic antigen, and negatively for CK20, CK7, prostate-specific antigen, and prostatic acid phosphatase. Both gastroscopy and colonoscopy failed to detect the primary tumor. An abdominopelvic CT scan was normal, but a CT scan of the chest disclosed a nodule measuring 2.5 x 1.5 cm in the lower lobe of the right lung. On bronchoscopy, it was found to be an invasive adenocarcinoma, consistent with a primary tumor of the lung. The patient was a heavy smoker (45 pack-years). The patient received 4 cycles of combined chemotherapy with carboplatine and gemcitabine, with no improvement. A month later, the patient complained of abdominal pain. Following demonstration of intra-abdominal spread of disease by CT scan, a second line chemotherapy was instituted with paclitaxel. A month later the patient's condition deteriorated and he complained of cough, sweating, and pain along the right leg. A bone scan revealed bone metastases in the right femur and left tibia. Two weeks later he was admitted to the hospital with intestinal obstruction and underwent laparotomy. He had massive intra-abdominal spread of cancer and ascites. Only a palliative colostomy was performed. The patient died 3 weeks later, 9 months after the diagnosis of adenocarcinoma of the lung. The clinical data on the three patients are summarized in Table I.

Infection with Kaposi's sarcoma-associated herpesvirus among families of patients with classic Kaposi's sarcoma.

BACKGROUND: Classic Kaposi's sarcoma (CKS) primarily affects elderly Mediterranean or Eastern European men. Incidence rates of CKS in Israel are among the world's highest. In practically all cases, antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) can be detected. A relatively high seroprevalence rate of KSHV in Israel generally correlates with the incidence of CKS. A sexual mode of virus transmission is recognized among homosexual men, whereas the precise transmission routes in the heterosexual population and those with CKS are still unclear. OBJECTIVE: To better assess the transmission routes of KSHV in Israeli patients with CKS and their first-degree relatives as compared with a control group. DESIGN: Serum was collected from all study participants and tested for KSHV antibodies by means of latent and lytic immunofluorescence assays. An open reading frame 65 (ORF65) Western blot assay was applied as a confirmatory tool. SETTING: Three dermatological departments in Israel. PATIENTS: Sixty-four Jewish patients with CKS, 143 of their first-degree relatives, and 186 hospital-based control subjects. RESULTS: Seropositivity to KSHV was detected in 62 (96.9%) of the patients with CKS, in 56 (39.2%) of their first-degree relatives, and in only 21 (11.3%) of the hospital controls (P<.001). The specific relationship with the index patient (spouse, offspring, or sibling) had no significant effect on the prevalence of serpositivity in the family members. CONCLUSION: Our serologic evidence of familial clustering of KSHV infection suggests a predominantly nonsexual horizontal transmission route of the virus.

Actinic damage among patients with psoriasis treated by climatotherapy at the Dead Sea.

BACKGROUND: Dead Sea climatotherapy is highly effective in the treatment of psoriasis. However, its potential side effects, especially the risk of skin cancer, are unclear. OBJECTIVE: We sought to determine the prevalence of solar damage and skin cancer among patients with psoriasis who underwent Dead Sea climatotherapy compared with control patients. METHODS: This multicenter controlled cross-sectional study was carried out at the Dead Sea Solarium Clinic and outpatient clinics of the participating centers. A total of 1198 participants (460 patients with psoriasis and 738 control patients) aged 20 to 70 years were included. A standard questionnaire including demographic parameters and sun exposure habits was administered to all participants. Patients were questioned about previous psoriatic treatments and climatotherapy at the Dead Sea. All participants underwent a structured physical examination of the skin. We compared the prevalence of solar damage for patients with psoriasis and control patients and assessed the extent of photodamage among patients with psoriasis according to exposure time at the Dead Sea in univariate and multivariate analyses. RESULTS: Elastosis ( P < .001), solar lentigines (P = .03), poikiloderma (P < .001), and facial wrinkles (P < .001) were significantly more common among patients with psoriasis compared with control patients and showed a dose response with increased Dead Sea exposure time. Self-reported previous skin cancers were more common in control patients compared with patients with psoriasis (8.2% vs 3.5%, P = .002), however, the prevalence of nonmelanoma skin cancer on examination did not differ between the two groups. No cases of malignant melanoma were detected in either group. CONCLUSIONS: Dead Sea climatotherapy is not associated with an increased risk of malignant melanoma or nonmelanoma skin cancer for patients with psoriasis in Israel. However, UV exposure at the Dead Sea may play a role in the development of solar damage.

Leishmania tropica in northern Israel: a clinical overview of an emerging focus.

BACKGROUND: In Israel, most cutaneous leishmaniasis (CL) is caused by Leishmania major. Recently a new focus of CL caused by Leishmania tropica has been described in Tiberias and the surrounding area of northern Israel. OBJECTIVE: The aim of this study was to evaluate clinical (size, number, location, and type of lesion) and laboratory (culture and polymerase chain reaction [PCR] analysis) parameters at diagnosis, response to treatment, and outcome of patients with CL due to L tropica. METHODS: Between September 2002 and March 2004, patients with direct smear-confirmed CL were evaluated; clinical records were reviewed and a telephone survey was performed. RESULTS: Forty nine patients, 34 (69%) male and 15 (31%) female, were studied. Mean age was 31.1 years (median 26 years, range 1-70); 76% of patients live in Tiberias and the surrounding area. The mean number of lesions was 2.6 (median 2, range 1-10). Lesions were commonly located on the face (61%) and upper limbs (57%). PCR analysis was performed in 27 patients and was positive for L tropica in 26. Fifty percent of patients studied received multiple therapeutic regimens because of incomplete response or treatment failure. Topical paromomycin was used in 44 patients (90%), with a complete response reported in only 17 (39%); of the 9 patients treated with intralesional sodium stibogluconate, a complete response was reported in 6 (67%); of the 5 patients treated with intravenous sodium stibogluconate, 4 (80%) were cured. LIMITATIONS: The relatively small number of patients studied combined with the fact that some were assessed retrospectively limit our conclusions. In addition, 50% of the patients studied received multiple therapeutic regimens because of failure of, or incomplete responses to, their initial therapy, thereby making comparisons difficult. CONCLUSIONS: The cure rate in those completing a course of antimony therapy, either 10 or more days of intravenous therapy or therapy administered intralesionally, was 75% (95% confidence interval [CI], 50.5-99.5%) as compared with 45% (95% CI, 28.9-60.5%) among those completing at least 10 days of topical paromomycin. To date, no standardized, simple, safe, and highly effective regimen for treating L tropica exists. Large, controlled clinical trials to evaluate current treatment regimens as well as new medications for CL, and especially CL attributed to L tropica, are urgently needed.

Mycetoma of the foot caused by Cylindrocarpon lichenicola in an immunocompetent traveler.

Cylindrocarpon is a cosmopolitan soil fungus, which rarely causes human disease. It has infrequently been reported as causing keratitis, mycetoma, osteomyelitis and peritonitis in chronic peritoneal ambulatory dialysis patients and disseminated infection in leukemic neutropenic hosts. This report describes a case of invasive infection caused by Cylindrocarpon lichenicola, localized in the right foot of an otherwise immunocompetent traveler.

An unusual co-occurrence of Langerhans cell histiocytosis and Rosai-Dorfman disease: report of a case and review of the literature.

BACKGROUND: The co-occurrence of Langerhans cell histiocytosis (LCH; disorder characterized by proliferation of Langerhans cells) and Rosai-Dorfman disease (RDD; histiocytic entity that is one of the non-Langerhans cell diseases) is extremely rare and raises several questions regarding the nature of the diseases. METHODS: We describe a 10-year-old boy who presented with a 3-month history of right scalp swelling. Clinical, pathological, and imaging evaluation disclosed multiple LCH of bone and cutaneous RDD. RESULTS: After initiating prednisone and vinblastine therapy, the patient developed an asymptomatic diffuse papular eruption. Biopsy revealed cutaneous RDD. Treatment was continued with a good response of bone LCH and significant amelioration of the cutaneous findings. CONCLUSIONS: Co-occurrence of LCH and RDD is a rare phenomenon. Various explanations, including the role of chemotherapy, are suggested based on our and several previously reported cases.