Bronchial asthma (BA), atopic dermatitis (AD), and allergic rhinitis (AR) are well known atopic disorders with complex etiologies. This study was undertaken to investigate the role of filaggrin, eosinophil major basic protein (MBP) and leukotriene B4 (LTB4) in patients with BA, AD, and AR. Sera from 1,246 patients with different atopic disorders and 410 normal healthy controls were collected and were evaluated for filaggrin, MBP and LTB4 by specific sandwich ELISAs, whereas immunoglobulin E (IgE) was used as a positive control for atopic patients. Serum analysis showed that filaggrin levels were remarkably high in patients with AD and in patients with multiple (mixed) atopic disorders (p < 0.001), whereas its levels in BA and AR patients were low but much higher than in normal human sera (p < 0.01). MBP levels were also high in AR, BA and mixed atopic patients, whereas AD patients showed no increase of MBP (p > 0.05). In contrast, LTB4 level was found to be significantly low in all tested atopic patients groups as compared to the levels of LTB4 present in normal human sera (p < 0.001). In conclusion, these findings support an association between filaggrin, MBP or LTB4 and atopic disorders. Our data strongly suggest that filaggrin, MBP or LTB4 might be useful in elucidating the mechanisms involved in the pathogenesis of these atopic disorders.
Abstract Netherton's syndrome (NS) is a rare autosomal recessive disease comprised of ichthyosis in the form of ichthyosis linearis circumflexa, hair shaft defects and atopic manifestations with an elevated IgE level. Various therapeutic options have been used in NS with variable success. Tacrolimus and pimecrolimus belong to the family of calcineurin inhibitors. They bind cytoplasmic proteins and the resulting complex binds calcineurin, inhibiting its ability to dephosphorylate the nuclear factor of activated T cells, thus suppressing gene transcription. There have been conflicting reports of the usefulness of tacrolimus in NS patients, with systemic absorption being the main adverse outcome. Here we report four Saudi siblings (two boys and two girls) with NS who were treated with topical tacrolimus and pimecrolimus with good control of their skin disease without any toxic effect. To our knowledge, this is the second report of the use of topical pimecrolimus in NS in the English literature.
Toll-like receptors (TLRs) are pattern-recognition-receptors that sense a variety of pathogens and initiation of innate and adaptive immune responses. This study was undertaken to investigate the expression of TLRs in peripheral blood-mononuclear cells (PBMCs) of AA patients and to determine whether TLR-mediated inflammatory signals are important for the perspective of AA management.Gene expression of TLRs and T-helper (Th) type-1, Th-2, Th-17 and regulatory T-cell cytokines in PBMCs was quantified by TaqMan Assays. Production of these cytokines in serum samples was determined by sandwich ELISAs.All TLRs (TLRs 1-10) were expressed in PBMCs of AA patients. Importantly intracellular TLRs (TLRs 3, 7, 8 and 9) were significantly up-regulated in AA patients as compared with controls (p < 0.05). Interleukin (IL)-2, TNF-α, and IL-17A gene expression in patients' PBMCs and their secretion in patients' sera were significantly higher as compared with their respective controls (p < 0.05). Whereas, TGF-β gene expression in patients' PBMCs and TGF-β protein level in patients' sera were significantly lower as compared with their controls (p < 0.05).This is the first report that shows the comprehensive expression profile of TLRs in AA patients. We conclude that up-regulated expression of intracellular TLRs in PBMCs of AA patients may play an active role in abnormal regulation of Th-1, Th-17 and regulatory T-cell cytokines in alopecia areata.Targeting of TLRs and their associated inflammatory signaling will open new areas of research; this may lead to the development of novel therapeutic targets for the treatment of AA or other skin disorders.
Pigmentary demarcation lines (PDL) are physiological abrupt transition lines between hyperpigmented skin and lighter areas. Recent evidence suggests that they involve the face.To survey facial PDL in Saudi females referred to general dermatology clinics for various complaints and determine any associated risks.Screening for facial lines was done in general dermatology clinics over a year. Whenever a patient was found to have facial PDL, a detailed questionnaire and examination were undertaken.Out of 1033 patients screened, 144 patients (14%) were found to have at least one of the facial PDLs. The median age of onset was 16 years. The most common line was F with 76 patients (53%). Family history was positive in 51 patients (35%).Facial PDL is a common and chronic pigmentary problem in Saudi women. It should be recognized and differentiated from other similar diseases like melasma. A significant proportion of patients have a milder presentation.
Staphylococcus aureus is known as a common pathogen in atopic dermatitis. A methicillin-resistant S. aureus strain with reduced susceptibility to vancomycin (VISA/VRSA) is increasing worldwide. The aims of this study were to evaluate the antibiotic-susceptibility pattern of S. aureus isolated from children with atopic dermatitis and to identify the occurrence of resistance to glycopeptide antibiotics.Swabs were collected from atopic dermatitis skin lesions of 80 children being treated at dermatology clinics whose ages ranged from 6 months to 15 years in the period from March 2009 to February 2010. Isolates were studied with an antibiogram for an antibiotic-susceptibility test. The selected antibiotics were the usually administered antimicrobials at dermatological clinics in Buraydah (Qassim, Saudi Arabia). Results were determined as minimal inhibitory concentration (MIC) using the Vitek system.Thirty S. aureus isolates showed resistance to streptomycin (100%), benzylpenicillin and ampicillin (96.7%), and oxacillin (90%). S. aureus resistance to trimethoprim/sulfamethoxazole, tigecycline, and vancomycin was 63.3%, 83.3%, and 53.3%, respectively. Resistance to linezolid was less, at 5.7%.Strains of MRSA with decreasing susceptibility to vancomycin were documented in the Qassim region of Saudi Arabia. Other studies will be required on VISA/VRSA strains concerning phenotypic and genotypic characterization.
To use intensive regimen of pulse steroid in the severe forms of Alopecia areata.This prospective randomized study was conducted at King Khalid University Hospital, Riyadh, Kingdom of Saudi Arabia between 2003 to 2009. Patients with Alopecia universalis, Alopecia totalis, or Alopecia ophiasis were assigned to one of the 3 treatment groups: Group A received oral mega pulse methylprednisolone (MP) for 3 consecutive days once every 2 weeks for 24 weeks; Group B received 2 consecutive daily pulses every 3 weeks; and Group C received 3 consecutive daily pulses every 3 weeks. Patients who showed regrowth of 75% or more at 24 or 36 weeks continued their treatment, while intervals were increased gradually.Forty-two patients were included in this study, and 52.4% of them had atopic diathesis, while 35.7% had autoimmune thyroiditis. At 36 weeks, 12 (28.6%) patients had adequate response, 9 (21.4%) had inadequate response, and 21 (50%) patients had poor response. The response rate shows no statistically significant difference between treatment groups. There were statistically significant differences in age of onset, duration of the disease, and presence of subclinical hypothyroidism between different response groups. At follow-up: 13 (38.2%) patients relapsed; 5 (14.7%) patients developed moderate hair fall; 3 (8.8%) patients developed mild hair fall; 7 (20.1%) patients maintained their hair regrowth; and 6 (17.6%) patients were lost follow up. It was relatively well-tolerated among groups B and C.Oral mega pulse MP use in severe forms of Alopecia areata has relative efficacy and tolerance but with high relapse rate.
Abstract: Scalp pruritus is a common complaint that is considered a diagnostically and therapeutically challenging situation. Scalp skin has a unique neural structure that contains densely innervated hair follicles and dermal vasculature. In spite of the recent advances in our understanding of itch pathophysiology, scalp itching has not been studied as yet. In this review, we summarize the current knowledge on the neurobiology of scalp and hair follicles as well as itch mediators and provide a putative mechanism for scalp itch with special emphasis on neuroanatomy and pathophysiology.
Background Patients with central centrifugal cicatricial alopecia (CCCA) often suffer from varying degrees of itch, pain and burning sensations. However, the neural component of these skin sensations has not been assessed. Objective To conduct a comprehensive analysis of C nerve fibre function relating to itch and pain perception in patients with CCCA using thermosensory testing and experimental itch models. Methods Fifteen healthy African-American women and 16 African-American female patients with CCCA participated in the study and underwent quantitative computerized thermosensory testing to assess warmth and heat pain thresholds. Itch was induced using histamine iontophoresis and application of cowhage spicules, and the intensity of each itch was assessed. The association between itch intensity and CCCA severity score was examined. Results A positive correlation between CCCA severity score and peak itch ratings of cowhage on the lesional scalp (crown) was observed (P = 0·023, r = 0·562). Notably, the histamine peak itch rating was not found to have a significant correlation with CCCA severity score (P = 0·913). The crown also had significantly higher warmth and pain thresholds than the occiput in both healthy subjects and patients with CCCA. Conclusions Our results suggest a putative role for the protease-activated receptor (PAR)-2, which is activated by cowhage, in the pathogenesis of CCCA. Future studies should examine PAR-2-directed therapeutics for patients with CCCA. Examining for itch and other dysaesthesias in patients with CCCA is of vital importance to dermatologists in assessing disease severity.
Background: β-lactam agents are known to elicit T-cell-mediated immune responses that play a central role in the onset of allergic reactions, but the involvement of specific type of cytokines in drug allergy remains largely unexplored in humans. Objectives: This study was undertaken to investigate the role of cytokines involvement in pediatric patients with β-lactam hypersensitivity and to determine whether involvement of cytokines in drug-mediated reactions are important for the perspective of allergic patient's management. Methods: β-lactam-induced hypersensitivity reactions in eighty pediatric patients were determined by clinical manifestations and skin prick or intradermal testing. Production of T-helper (Th) type-1 cytokine interferon (INF)-γ, Th-2 cytokine interleukin (IL)-4, regulatory T-cell cytokine IL-10, and other cytokines IL-6 and IL-12 were determined by sandwich ELISAs. Results: Diagnosis of β-lactam allergy was confirmed in 53 pediatric patients. IL-4 secretion in patients' sera was significantly higher as compared with healthy controls (P < 0.05). However, INF-γ level in patients' sera was significantly lower as compared with controls (P < 0.05). No significant alterations were found in the protein secretion of IL-10, IL-12, and IL-6 in allergic patients as compared with controls (P > 0.05). Conclusion: We conclude that IL-4 is specific marker for the diagnosis of β-lactam-induced hypersensitivity. Moreover, IL-4 in combination with INF-γ is more sensitive for the diagnosis of these reactions. This study also concludes that both IL-4 and INF-γ may play an active role in the onset of allergic reactions against β-lactam antibiotics.