Possible role of plasmacytoid dendritic cells in pityriasis lichenoides.

BACKGROUND: Plasmacytoid dendritic cells (pDCs) and their product, type I interferons (IFNs), have been implicated in the pathogenesis of several skin disorders characterized by an interface dermatitis (ID) pattern, such as lichen planus (LP). A type I IFN signature has previously been documented in pityriasis lichenoides (PL). Although pDCs are known to be the main source and most potent producers of local type I IFNs, their role in PL has not been investigated. AIM: To investigate the role of pDCs in PL. METHODS: In total, 20 cases of PL and 20 comparable cases of LP were immunohistochemically tested for pDC occurrence and type I IFN production using anti-blood-derived dendritic cell antigen-2 (BDCA2; a specific pDC marker) and anti-myxovirus protein A (anti-MxA) antibodies (indirect marker of pDC activity), respectively. MxA is a well-established surrogate marker for local type 1 IFN production. A semiquantitative scoring system was used. RESULTS: pDCs were present in all 40 cases with no statistically significant difference between the two groups. MxA expression was intense and diffuse in the majority of PL and LP cases. CONCLUSIONS: pDCs constitute a central component of the inflammatory infiltrate in PL, suggesting that PL shares with the other entities that exhibit an ID a common pDC-driven process through type I IFN production, which ultimately leads to the cytotoxic attack.

Erythropoietic protoporphyria a clinical and molecular study from Lebanon: Ferrochelatase a potential tumor suppressor gene in colon cancer.

Erythropoietic protoporphyria (EPP) is a rare cutaneous and systemic disease caused by mutations in the ferrochelatase gene (FECH). The molecular underpinnings of EPP in Middle Eastern populations and relative to other ethnic groups secondary to increased consanguinity are unknown. To understand the molecular pathogenesis of Middle Eastern EPP, we surveyed clinicopathological and molecular features in 6 large consanguineous families from Lebanon and Syria presenting with cutaneous and systemic features consistent with EPP. We observed 30% increased liver disease and 20% elevated end-stage liver complications in our EPP cohort compared to EPP patients previously reported elsewhere. In addition, Middle Eastern EPP patients in our cohort exhibited uniquely an increased incidence of colon cancer. Sequence analysis revealed 2 novel non-synonymous FECH mutations in the studied families designated p.M294T and p.I230M. In addition, FECH activity was significantly decreased (6%) in fibroblasts obtained from sun-exposed sites in a patient with p.M294T mutation, whereas in sharp contrast, protected sites from the same patient exhibited 54% activity for the gene. We also found that sun-exposed fibroblasts, relative to sun-protected and control fibroblasts, exhibited suppressed growth and atypical morphology in vitro, and that these effects were alleviated when the cells were co-cultured with sun-protected fibroblasts. Our findings on the increased incidence of colon cancer in EPP patients prompted us to survey FECH expression patterns in cancer. Using publicly available microarray datasets we found that FECH mRNA was largely significantly decreased in colon adenocarcinomas relative to normal colon tissues. Our findings suggest that families with autosomal recessive EPP should be screened more extensively for systemic involvement including liver diseases and colon cancer, and point to a previously unknown yet plausible tumor suppressor role for FECH in colon malignancy.

Managing acne in the Middle East: consensus recommendations.

Acne has been estimated to affect the majority of people at some point in their life and is common in Middle Eastern countries. While acne is frequently perceived to be a self-limited disease of adolescence, there is an increasing population of adults with acne. Information about the management of acne in the Middle East is somewhat sparse; however, several studies have recently been conducted and will be discussed in this supplement.

Plasmacytoid dendritic cells in alopecia areata: missing link?

BACKGROUND: Type I interferon (IFN) signature has been implicated in alopecia areata (AA). However, type I IFN source has never been documented. Plasmacytoid dendritic cells (PDCs) are generally known to be the main source and most potent producers of local type I IFNs. Their role in AA pathogenesis has never been investigated. OBJECTIVE: Investigate PDC role in AA. METHODS: Nineteen AA cases were retrieved from our database and were immunohistochemically tested for PDC occurrence and activity using anti-BDCA-2 and anti-MxA antibodies respectively. Comparison to 10 trichotillomania and 7 androgenetic alopecia (AGA) cases was also done. RESULTS: Plasmacytoid dendritic cells were present in all AA cases in a peri-bulbar location and, as indirectly assessed by MxA expression, were in an active state producing type I IFNs. All trichotillomania cases showed the presence of PDCs, though significantly less abundant and in a different distribution (mainly superficial perivascular) than that in AA. PDC presence and MxA expression were absent in AGA. CONCLUSIONS: Plasmacytoid dendritic cells constitute a central component of the peribulbar infiltrate in AA suggesting a significant role in AA pathogenesis. Additionally, PDC distribution could help in microscopically differentiating AA from trichotillomania or AGA.

BRAF mutation status in primary and metastatic melanomas in two regions with differing potential ultraviolet radiation exposure.

BACKGROUND: Melanoma is seen as a heterogeneous molecular entity, with solar ultraviolet radiation (UVR) and BRAF mutation status being important determinants. AIM: To study primary and metastatic melanomas from two UVR-distinct regions to elucidate correlations between prognostic predictors, UVR and BRAF mutation status. METHODS: Extended BRAF testing for 9 mutations was obtained for 95 primary melanomas [Lebanon (LB) n = 55, Pakistan (PK) n = 40)] and 65 metastatic melanomas (LB n = 36, PK n = 29). Collected data included patient age and sex, melanoma size and anatomical location, prognostic parameters and solar elastosis grade for primary melanomas. For metastatic melanomas, site of metastasis, magnitude of necrosis and degree of pigmentation were assessed. Cumulative 21-year averages of potential UVR exposure for Lebanon (110 kJ/m(2) /year) and Pakistan (128 kJ/m(2) /year) were derived from the National Center for Atmospheric Research databases. RESULTS: BRAF mutation status was obtained for 146/160 cases (91.3%). Overall mutation rate was 24/88 (27.3%) in primary and 25/58 (43.1%) in metastatic melanoma. V600E was the predominant mutation in 21/24 (87.5%) of primary and 23/25 (92%) of metastatic melanomas. A 60% discordant mutation rate was identified; of three patients, two lost the mutation in the metastasis and one gained it. The relative incidence of BRAF mutation with potential UVR exposure showed a similar trend in primary (low vs. high UVR: 32.1% vs. 20.0%) and metastatic (57.1% vs. 21.7%) melanomas (P < 0.05). Predictors of BRAF mutations were trunk location and epithelioid and mixed cytology for primary and subcutaneous metastasis, low UVR exposure and absence of pigmentation for metastatic melanomas (P < 0.05). BRAF-positive status in primary melanomas was predicted by multivariate binary logistic regression with reasonable accuracy (C-statistic = 0.67, 95% CI 0.530-0.81 with one independent predictor, namely, epithelioid cytology (OR = 5.11, 95% CI 1.38-8.88, P = 0.01). In metastatic melanomas, high UVR (OR = 0.21, 95% CI 0.06-0.07; P < 0.01) was an independent negative predictor of BRAF mutation. CONCLUSIONS: We have documented the rate of different BRAF mutation types in a Lebanese and Pakistani cohort, and assessed correlations with prognostic markers and potential UVR exposure.

Clinicopathological study of 81 cases of localized and systemic scleroderma.

BACKGROUND: Scleroderma is a connective tissue disease that includes localized and systemic forms. Our recent encounter with a morphea case exhibiting prominent perineural inflammation microscopically prompted us to assess the features of all patients diagnosed with morphea/scleroderma at our institution. OBJECTIVE/METHODS: To describe the clinicopathological features of all patients diagnosed with morphea/scleroderma at American University of Beirut Medical Center (AUB-MC) between 1999 and 2010, and compare our findings with those published in the literature. RESULTS: A total of 81 cases (63 women and 18 men) were identified, of which 73 were localized (morphea) and eight were systemic scleroderma. Clinically, plaque type morphea was the most common variant both in adults and children, and seven (9%) cases of morphea were associated with lichen sclerosis et atrophicus (LSA). Histopathologically, perineural inflammation was observed in 49% of cases, and may serve, in addition to other features including lichen sclerosis-like changes (observed in exclusively nine cases of morphea), more diffuse dermal and less subcutaneous sclerosis, and intense inflammation, as clues favouring diagnosis of morphea over systemic sclerosis. CONCLUSION: The features of morphea/scleroderma patients in this study are generally comparable to those published in the literature, with few differences. Clinically, plaque type morphea was the most common variant both in adults and children and LSA was a frequent association. Histopathologically, perineural inflammation was commonly observed and may serve in addition to lichen sclerosis-like changes and intense inflammation as clues favouring diagnosis of morphea over systemic sclerosis.

Confluent and reticulated papillomatosis: clinical and histopathological study of 10 cases from Lebanon.

BACKGROUND: Confluent and reticulate papillomatosis (CRP) is a rare disorder that has mostly been described in case reports and limited case series. Studies on this condition from our region are lacking. OBJECTIVE/METHODS: To describe the clinical and histopathological findings, as well as response to treatment of all patients diagnosed with CRP at the American University of Beirut Medical Center (AUB-MC) between 1999 and 2009, and to compare our findings with those published in the literature. RESULTS: Confluent and reticulate papillomatosis was diagnosed in 10 patients (five men, five women). Mean age at diagnosis was 19 years. Duration of lesions ranged from few months to several years. Skin lesions mainly consisted of reticulated, pigmented macules, patches and plaques. The most common area of involvement was the chest in five cases. The rash was asymptomatic in eight patients. Skin biopsy specimens from all patients revealed hyperkeratosis, papillomatosis and variable acanthosis. Whereas follicular plugging was observed in nine cases, anastomosis of the rete ridges was noted in three. Periodic acid Schiff stains highlighted yeast forms in six cases. CONCLUSION: The clinical and histopathological features of the CRP patients in our study are generally comparable to those published in the literature, with minor differences. Clinically, one case had an atypical clinical presentation, and microscopically follicular plugging was seen in the majority of cases. Yeast-like spores were seen in six cases further supporting a role of Malassezia furfur in the pathogenesis of CRP.

Chronic cutaneous leishmaniasis, a great mimicker with various clinical presentations: 12 years experience from Aleppo.

BACKGROUND: Cutaneous leishmaniasis (CL) has been an endemic disease in Aleppo, Syria for many decades. During the past 12 years, there was a clear increase in the overall incidence of the disease in the region. Treatment using intralesional method of antimonial compounds became ineffective in a considerable proportion of cases and more patients developed the chronic form of the disease. OBJECTIVES: To categorize chronic cutaneous leishmaniasis (CCL) into different subtypes that mimic a wide spectrum of skin diseases, and to analyse the cause of this increase in the incidence of the disease as a whole and of the chronic type in particular. METHODS: A total number of 6200 patients with CL were seen in our centre, among which 1880 were initially diagnosed with CCL. Inclusion criteria for CCL included CL for more than 1 year. The diagnosis of CCL was made based on the clinical presentation and a positive Giemsa smear test. Biopsies were performed whenever the Giemsa smear was negative. Patients who had immunosuppression due to a medical condition or intake of immunosuppressive medications were excluded. RESULTS: Of 1880 patients, 1750 patients fit the inclusion criteria. Based on the lesion morphology, three different types of CCL were defined, among which five subtypes were observed based on clinical pattern and distribution of lesions. The two most common types of CCL were the papulonodular and plaque forms. Around 80% of all CCL cases occurred in individuals under 16 years of age and the most common location was the face (88.6% of cases). CONCLUSIONS: CCL due to Leishmania tropica can mimic many other dermatological conditions which might lead to a delay in making the correct diagnosis resulting in increased resistance to treatment. We have illustrated eight different clinical presentations of CCL and their differential diagnoses to make physicians more aware of the atypical presentations of CCL. A new treatment plan is suggested for the high-risk group of acute cutaneous leishmaniasis patients to decrease the likelihood of progressing to chronicity.

Cutaneous non-tuberculous Mycobacterial infections: a clinical and histopathological study of 17 cases from Lebanon.

BACKGROUND: Only a few studies characterized cutaneous non-tuberculous Mycobacterium (NTM) infections in this region of the world. Objective The aim of this study was to describe the epidemiological, clinical and histological findings of cutaneous NTM infections in Lebanon. PATIENTS/METHODS: Retrospective study of 17 patients (19 histological specimens) diagnosed with cutaneous NTM infections and confirmed by culture-based partial sequencing of the 16S rRNA gene at the American University of Beirut Medical Center between 2005 and 2008. RESULTS: Of 17 cases, 14 were caused by Mycobacterium marinum. All patients were immunocompetent except for one. Clinically, the most common presentation was multiple sporotrichoid lesions over an extremity (8/17). Many patients had peculiar presentations including bruise-like patches, herpetiform lesions, annular ulcerated plaques, symmetrical nodules over the buttocks and locally disseminated lesions with surrounding pale halo. Almost all patients cleared their infection on either minocycline or clarithromycin monotherapies. Histologically, a dermal small vessel proliferation with mixed inflammation (granulation tissue-like changes) was identified in 58% of specimens. The most common type of granulomatous inflammation was the suppurative (47%) followed by the tuberculoid (30%), sarcoidal (11%), and palisading (5%) types. Lichenoid granulomatous dermatitis was noted in 42% of cases. Special staining highlighted mycobacteria in only two specimens. CONCLUSIONS: The incidence of cutaneous NTM infections is high in our area. Many patients had peculiar clinical presentations. Our study is the second to report the common presence of granulation tissue-like changes as a good histological indicator of cutaneous NTM infections. Minocycline and clarithromycin remain the drugs of choice in our area.

Survey of acne-related post-inflammatory hyperpigmentation in the Middle East.

Aim: Acne vulgaris is a common inflammatory skin disease in the Middle East, similar to other regions of the world. In the Middle East, there are a relatively large proportion of patients with darker pigmentation (Fitzgerald skin types III-VI) who are prone to developing post-inflammatory hyperpigmentation (PIH) as a sequela of acne. Data are sparse on the frequency and characteristics of PIH throughout the world. What information is available indicates that pigmentation problems can be very bothersome for patients and are often quite long-lasting. Thus, it is important for clinicians to be aware of the scope of the problem of acne-associated PIH as well as potential treatment options. Methods: Prospective non-interventional study of acne patients consulting dermatologists (n = 262) in the Middle East. Results: PIH was present in 87.2% of subjects. The majority of subjects (52.6%) reported that PIH had been present for one year or longer. Of note, 69.0% of subjects reported excoriating their acne lesions, suggesting that this may be a key modifiable risk factor for clinicians to stress during patient education efforts. Conclusions: PIH was bothersome for patients, with half of subjects indicating that PIH was more bothersome than acne. In addition to our study results, we present here a brief overview of PIH and its treatment.

193 nm excimer laser selective ablation of in vivo guinea pig epidermis.

We have previously shown that 193 nm excimer laser irradiation cleanly and effectively ablates avascular tissue with minimal thermal damage to surrounding adjacent structures. In this study, the 193 nm excimer laser is used to remove guinea pig epidermis in vivo. The epidermis can be totally ablated with thermal damage extending only superficially into the dermis. Reepitheliazation of the ablated area takes place in 1 week or less. This technique may be applicable to the removal of benign epidermal lesions.

Ultraviolet excimer laser ablation: the effect of wavelength and repetition rate on in vivo guinea pig skin.

Multiple dermatologic conditions that are currently treated with traditional cold-knife surgery are amenable to laser therapy. The ideal surgical treatment would be precise and total removal of abnormal tissue with maximal sparing of remaining structures. The ultraviolet (UV) excimer laser is capable of such precise tissue removal due to the penetration depth of 193 nm and 248 nm irradiation of 1 micron per pulse. This type of ablative tissue removal requires a high repetition rate for efficient lesional destruction. Excimer laser radiation at 193 nm is capable of high repetition rates, which are necessary while 248 nm radiation causes increasing nonspecific thermal injury as the laser repetition rate is increased.

Hyperkeratosis of the nipple and areola: report of 3 cases.

BACKGROUND: To date, approximately 43 cases of hyperkeratosis of the nipple and areola have been reported, most of which have been sporadic. OBSERVATION: We describe 3 patients with this dermatosis who were encountered in the outpatient clinic of the Department of Dermatology at the American University of Beirut Medical Center, Beirut, Lebanon, within a 1-year period. CONCLUSION: Hyperkeratosis of the nipple and/or areola may be more common than what has been reported in the literature. We propose a revised classification for the condition.