Scaly erythematous eruptions of intertriginous locations.

Intertriginous or flexural eruptions are common presenting problems in clinical practice, raising several differential diagnoses. A clinico-histopathological correlation is important to establish a correct diagnosis when a clinical diagnosis cannot be ascertained. We here present a case of flaky erythematous eruptions in a female adult, with a final diagnosis of granular parakeratosis, involving nonflexural area mid-back (under bra cover) in addition to flexural zones of the groin, gluteal fold, inframammary fold and axilla. It seems that mechanism of pressure and friction as well as occlusion all play a part. Management with potent topical steroid and avoidance of inciting triggers offered resolution in 4 weeks in this case.

Frontal Fibrosing Alopecia. An Example of Disrupted Aryl Hydrocarbon Receptor-Mediated Immunological Homeostasis in the Skin?

Sun protection has been recommended by public health authorities to reduce the risk of keratinocyte and melanocyte tumors, yet some sun exposure is required for vitamin D synthesis. Frontal fibrosing alopecia (FFA) is a cicatricial alopecia that has been reported to have an association with facial photoprotection. The brief review proposes the hypothesis that FFA arises as a result of excessive facial photo-protection with a resultant disturbance in immunological homeostasis mediated via the aryl hydrocarbon receptor-kynurenine pathway axis (AHR/KP) leading to the collapse of immune privilege at the hair bulge.

Assessing the response of morphea and limited scleroderma to tranilast: a small prospective study comparing topical corticosteroids to a combination of topical corticosteroids and tranilast.

BACKGROUND: Scleroderma is traditionally managed with immunomodulatory agents such as methotrexate, mycophenolate mofetil and corticosteroids. There are anecdotal reports for, and theoretical reasons why, the anti-fibrotic agent tranilast may provide an additional treatment modality. OBJECTIVE: The objective of the current study was to demonstrate if the addition of topical tranilast to an established regime resulted in an improvement in the Localized Scleroderma Assessment Tool (LoSCAT) and modified Rodnan score. PATIENTS AND METHODS: A small double-blinded randomized prospective study of 11 pairs of treatment sites in four patients; three with morphea and one with limited scleroderma was performed. All patients continued with their prescribed treatment and applied 0.1% betamethasone valerate in PCCA PracaSil™ (B) to the control site with 0.1% betamethasone valerate and 1% tranilast (B/T) to the comparator site over a period of 3 months. Photographs and monthly LoSCAT scores were performed on the morphea patients and a modified Rodnan score on the limited scleroderma patient. Statistical analysis was via sign test. RESULTS: The mean baseline LoScat score at the B treated sites was 6.6 which improved to 4.3 (p= 0.16). The mean baseline LoScat score at the B/T treated sites was 5.75 which improved to 2.8 following treatment. (p=0.04). LIMITATIONS: This was a small single center study. The ideal concentration of tranilast is unknown. As all patients continued with standard management the expected response may be less than would have been anticipated in a single agent trial. CONCLUSION: The role of tranilast in the management in scleroderma warrants further investigation in larger trials.

Atypical presentation of livedo racemosa in a factor V Leiden heterozygous positive patient with Pseudomonas aeruginosa urosepsis.

Impairment of the protein C pathway, detectable by reduced plasma levels of activated protein C (APC), are risk factors for venous thrombosis. Activated protein C maintains clotting homeostasis by regulation of pro-coagulant factors Va and VIIIa. Both infection and the factor V Leiden mutation reduce the formation of APC from protein C in the blood. With low levels of APC, excess factors Va and VIIIa exist, increasing the risk of thrombus formation. Livedo racemosa is characterised by a striking, violaceous branch-like pattering of the skin. It is similar to livedo reticularis, but with a different morphology and histopathology. In this case report we present the first case of livedo racemosa, in an 89-year-old factor V Leiden-positive patient with a Pseudomonas aeruginosa urinary tract infection. The cutaneous biopsies demonstrated vasculopathy with intraluminal thrombi in subcutaneous vessels with no evidence of inflammatory vasculitis.

The aryl hydrocarbon receptor: a review of its role in the physiology and pathology of the integument and its relationship to the tryptophan metabolism.

The aryl hydrocarbon receptor (AHR) is a cytosolic receptor for low molecular weight molecules, of which the most widely recognized ligand is 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and the most widely recognized effect, chloracne. Adverse effects of manipulation were most recently and graphically demonstrated by the poisoning of Viktor Yushchenko during the Ukrainian presidential elections of 2004. However, recent research has revealed a receptor with wide-ranging, and at times, paradoxical actions. It was arguably among the first biological receptors to be utilized by dermatologists, dating from the time of topical tar preparations as a therapeutic agent. I provide a review outlining the role AHR plays in the development, cellular oxidation/antioxidation, responses to ultraviolet light, melanogenesis, epidermal barrier function, and immune regulation and its relationship to tryptophan metabolism. Finally, I will review the role of AHR in diseases of the integument.

Effects of tranilast on the urinary excretion of kynurenic and quinolinic Acid under conditions of L tryptophan loading.

The pathogenesis of morphea and other cutaneous sclerosing disorders remain poorly understood. Although they are considered to be autoimmune disorders, abnormal tryptophan metabolism may be involved. Current therapy is directed to supressing the autoimmune response. Demonstration of a therapeutic response to manipulation of the kynurenine pathway would both support a role for abnormal tryptophan metabolism and offer additional targets for therapy. Tranilast is a 3-hydroxyanthranilic acid derivative known to target the kynurenine pathway. The aim of this study was to see if tranilast lowered the urinary excretion of the kynurenine metabolites kynurenic and quinolinic acid under condition of L tryptophan loading in a volunteer. Mean baseline value for kynurenic acid and quinolinic acid were 1.1 and 2.1 mmol/mol creatinine, respectively. This rose to 5.6 and 3.8 mmol/mol creatinine respectively under conditions of L tryptophan loading 2 grams daily. Adding 1 g of tranilast daily lowered the values to 2.0 and 2.9 mmol/mol creatinine, respectively. These data suggest that tranilast acts as a competitive inhibitor of either indoleamine 2, 3-dioxygenase (IDO), tryptophan 2, 3-di-oxygenase (TDO) or both. As it involved only 1 subject, the results may not be representative of the larger population and must be considered preliminary.

Immunohistochemical studies of the kynurenine pathway in morphea.

Cutaneous sclerosis, resembling that seen in subcutaneous morphea, is a feature of eosinophilic fasciitis and eosinophilia-myalgia syndrome, two conditions in which the kynurenine pathway is known to be activated. To investigate the possibility of activation of the kynurenine pathway in morphea, skin biopsies were taken from involved and non-involved sites in a series of three patients with morphea. Immunohistochemical stains for quinolinic acid and indoleamine 2,3-dioxygenase (IDO) were performed.

Köbnerization in a woman with generalized lichen sclerosus.

A 52-year-old woman presented with an 18-month history of genital and extragenital lichen sclerosus. In addition to the classical genital findings, lesions of lichen sclerosus were present over her back, chest and the medial aspect of her right thigh and leg. On her right thigh and extending to her right leg, lesions of lichen sclerosus displaying the Köbner response were noted over the course of a varicosed long saphenous vein. There were no features of varicose dermatitis in the region displaying the Köbner response. It is proposed that the ambulatory venous pressure within the vein acted as a stimulus for the Köbner response.

Granulomas in common variable immunodeficiency: a diagnostic dilemma.

A 60-year-old man with common variable immunodeficiency presented with a 7-year history of violaceous plaques and papules on the thighs, arms and trunk. In the preceding 2 years he had developed new lesions on both hands. He had been previously diagnosed with sarcoidosis on the basis of skin and visceral histology, but subsequent opinion was that these were sarcoid-like granulomas rather than being representative of true sarcoidosis. Biopsy of the hand lesions showed necrotizing granulomas, and a single acid-fast bacillus (AFB) was identified on Wade-Fite stain. Subsequent repeat tissue biopsies for histology, culture and polymerase chain reaction testing failed to confirm the presence of mycobacterial organisms and it was felt that the organism was a contaminant introduced during tissue processing. The hand lesions responded well to intralesional injections of triamcinolone acetonide 10 mg/mL and oral tetracycline 500 mg b.d. was later introduced with a good clinical response. The diagnostic dilemma of finding granulomatous inflammation in a patient with common variable immunodeficiency, and the significance of a single AFB on histology are discussed. The treatment of sarcoid-like granulomas with tetracycline therapy is also commented on.