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.

Infantile haemangiomas and quality of life.

OBJECTIVE: To determine the quality of life (QOL) and self-esteem of children with infantile haemangiomas using objective measures. DESIGN: Twenty-one children, 5-8 years old, with a diagnosis of head or neck haemangioma measuring 2 cm or more, were compared with 22 children with no history of haemangioma. SETTING: A tertiary medical centre in the north of Israel. INTERVENTIONS: Demographic and clinical details were collected, followed by two questionnaires-Paediatric Quality of Life Inventory (PedsQL) and Harter pictorial scale of Perceived Competence and Social Acceptance for young children-answered by children and parents of the two groups. MAIN OUTCOME MEASURES: QOL and self-esteem of the children in the two groups. RESULTS: There were no significant differences in QOL indices or self-perception scores between children with and without haemangioma (86.6±10.3 vs 80.1±15.07, p=0.23 and 3.62±0.2 vs 3.72±0.21, p=0.17, respectively). Interestingly, parents of children with haemangioma reported higher QOL of their children than parents of children without haemangioma (86.4±9.6 vs 77.1±14.9, p<0.03). Likewise, a positive correlation between parents' scored PedsQL and children's scored PedsQL was found (0.56, p=0.008). CONCLUSIONS: The findings raise a question about aggressive as opposed to more conservative treatment, especially in the era of propranolol.

Participation in leisure activities and sensory modulation deficiencies of children with atopic dermatitis.

AIM: To examine whether the complexity of atopic dermatitis (AD) symptoms and the sensory modulation deficiencies (SMD) that accompany it may limit child's preference to participate in leisure activities. METHODS: Thirty-seven children diagnosed with AD and 104 healthy peers aged 6-11 years participated in this study. Disease severity was assessed using SCORAD scores. Both groups were compared in regard to their sensory modulation abilities measured by the 'Short Sensory Profile' (SSP) and in regard to their activity preference measured by the 'Preference for Activities of Children' (PAC). RESULTS: Children with AD showed lower preference to participate in leisure activities as compared with healthy peers (F = 4.63, p < 0.0001). Among children with AD, significant correlations were found between SMD in several modalities and preference to participate in specific leisure activities. No significant correlations were found between AD severity and the child's preferred activities. CONCLUSIONS: Children with AD may show lower preference to participate in activities in comparison with their typical peers. This lower preference may be impacted by their SMD. Multidisciplinary intervention may be beneficial for children with AD. This intervention should refer to AD symptoms and considers the child's sensory profile and participation in daily living.

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.

Alopecia, neurological defects, and endocrinopathy syndrome caused by decreased expression of RBM28, a nucleolar protein associated with ribosome biogenesis.

Single-gene disorders offer unique opportunities to shed light upon fundamental physiological processes in humans. We investigated an autosomal-recessive phenotype characterized by alopecia, progressive neurological defects, and endocrinopathy (ANE syndrome). By using homozygosity mapping and candidate-gene analysis, we identified a loss-of-function mutation in RBM28, encoding a nucleolar protein. RBM28 yeast ortholog, Nop4p, was previously found to regulate ribosome biogenesis. Accordingly, electron microscopy revealed marked ribosome depletion and structural abnormalities of the rough endoplasmic reticulum in patient cells, ascribing ANE syndrome to the restricted group of inherited disorders associated with ribosomal dysfunction.

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.

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.

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.

Subcutaneous panniculitic T-cell lymphoma in children: response to combination therapy with cyclosporine and chemotherapy.

We describe 2 adolescent boys with facial swelling and/or subcutaneous nodules and fever. Extensive evaluation, including several biopsy specimens, led to a diagnosis of subcutaneous panniculitic T-cell lymphoma, an entity rarely seen in children. Both patients were treated with oral cyclosporine in an effort to suppress the cytokine release from T-cells that has been thought to induce the hemophagocytic syndrome. The patients responded dramatically to cyclosporine treatment with defervescence of the fever and reduction in number and size of the subcutaneous nodules. Subsequent therapy with multidrug chemotherapy achieved complete remission in the first patient. This report suggests the value of cyclosporine as a first-line agent coupled with chemotherapy in the treatment of patients with subcutaneous panniculitic T-cell lymphoma. A clinicopathologic review of 8 described pediatric cases of subcutaneous panniculitic T-cell lymphoma is also presented.

A child with both Langerhans and non-Langerhans cell histiocytosis.

The histiocytic syndromes consist of a group of disorders that share in common the proliferation of cells of the monocytic/macrophage lineage. It has been conventional to divide the histiocytoses into two separate groups: Langerhans cell histiocytosis (LCH) and non-LCH. We present a 2-year-old Hispanic boy who was referred to the dermatology clinic for evaluation of an asymptomatic cutaneous eruption of the head and upper trunk. In addition, he had a 3-week history of pain in his right leg and difficulty in walking. The patient's physical examination was normal, excluding the skin findings. On plain radiography, multiple lytic lesions in the skull, lumbar spine, and right tibia were seen. Histopathologic examination of a skin biopsy specimen revealed a predominantly histiocytic infiltrate in the dermis which was negative for S-100 and CD1a stains. A tibial biopsy specimen showed a monomorphous infiltrate of histiocytes that were S-100 and CD1a positive. This patient's concomitant findings of both LCH and non-LCH histiocytoses further support a potential overlap within the histiocytic syndromes, as has been suggested by others.