Treatment of granuloma annulare and related granulomatous diseases with sulphasalazine: a series of 16 cases.

BACKGROUND: Granuloma annulare (GA) and the related annular elastolytic giant cell granuloma (AEGCG) and interstitial granulomatous dermatitis (IGD) are idiopathic histiocytic inflammatory disorders, which are frequently recalcitrant to treatment. OBJECTIVES: Evaluate the efficacy of sulphasalazine in treating GA, AEGCG and IGD. METHODS: Sixteen patients were identified with granulomatous disease who were treated with sulphasalazine between September 2015 and September 2019. Outcomes were based on patients' and providers' subjective evaluations. RESULTS: Sixteen patients were included in the study (ages 56-89, four male and twelve female). Previous treatments were attempted in fifteen patients. Clinical improvement was seen in fourteen patients (87.5%). Initial improvement was noted within a mean (SD) of 66.4 (35.1) days after starting therapy, with increasing benefits over time. Ten patients (62.5%) reported complete or near-complete clearance, three patients (18.8%) reported significant improvement, and one (6.3%) reported partial improvement. Twelve patients elected to stop or reduce therapy, resulting in relapse or worsening in five patients. CONCLUSIONS: Sulphasalazine may be considered as treatment for GA and GA-related conditions.

Abnormal sweating patterns associated with itching, burning and tingling of the skin indicate possible underlying small-fibre neuropathy.

BACKGROUND: Itching, burning, numbness and tingling of the skin are frequent reasons for dermatology consultation. We hypothesized that these sensations may be attributable to a small-fibre neuropathy. Sweating, which is mediated by small nerve fibres, may be a surrogate marker of small-fibre neuropathy. OBJECTIVES: To investigate the results of thermoregulatory sweat testing (TST), which depicts and estimates whole-body sweating, in patients with itching, burning, numbness and tingling sensations. METHODS: We retrospectively reviewed the medical records of 227 patients with itching, burning, numbness and tingling sensations involving the skin who were seen at our institution during 2008 and also underwent TST. RESULTS: The mean age of the cohort was 54 years (range 3-89), and 58% were female. In all, 149 patients (66%) had abnormal TST results; in 119 (80%) of these patients the areas of anhidrosis on TST corresponded to their symptomatic areas. For each symptom analysed separately, the area of anhidrosis correlated with the area of symptoms in most patients. CONCLUSIONS: Patients with burning, itching, numbness and tingling have abnormal sweating patterns and often do not sweat in the symptomatic areas. These novel findings suggest that a small-fibre neuropathy may underlie many cutaneous symptoms and that the neuropathy can be estimated using TST.

A population-based study of the incidence of delusional infestation in Olmsted County, Minnesota, 1976-2010.

BACKGROUND: Delusional infestation (DI) is a well-recognized clinical entity but there is a paucity of reliable data concerning its epidemiology. Knowledge of the epidemiology is fundamental to an understanding of any disease and its implications. Epidemiology is most accurately assessed using population-based studies, which are most generalizable to the wider population in the U.S. and worldwide. To our knowledge, no population-based study of the epidemiology (particularly incidence) of DI has been reported to date. OBJECTIVES: To determine the incidence of delusional infestation (DI) using a population-based study. METHODS: Medical records of Olmsted County residents were reviewed using the resources of the Rochester Epidemiology Project to confirm the patient's status as a true incident case of DI and to gather demographic information. Patients with a first-time diagnosis of DI or synonymous conditions between 1 January 1976 and 31 December 2010 were considered incident cases. RESULTS: Of 470 identified possible diagnoses, 64 were true incident cases of DI in this population-based study. The age- and sex-adjusted incidence was 1·9 [95% confidence interval (CI) 1·5-2·4] per 100 000 person-years. Mean age at diagnosis was 61·4 years (range 9-92 years). The incidence of DI increased over the four decades from 1·6 (95% CI 0·6-2·6) per 100 000 person-years in 1976-1985 to 2·6 (95% CI 1·4-3·8) per 100 000 person-years in 2006-2010. CONCLUSIONS: Our data indicate that DI is a rare disease, with incidence increasing across the life span, especially after the age of 40 years.

Mutations in the rod domain of keratin 2e in patients with ichthyosis bullosa of Siemens.

Ichthyosis bullosa of Siemens (IBS) is an autosomal dominant skin disorder that resembles epidermolytic hyperkeratosis (EHK). We have identified mutations in two families originally diagnosed with EHK and in four families diagnosed with IBS at the same codon in the highly conserved carboxy terminal of the rod domain of keratin 2e, thus revealing a mutational hot spot. Our results allow a differential diagnosis to be made between IBS and EHK at the genetic level and we suggest that patients diagnosed with EHK, but lacking keratin K1 or K10 mutations, should be re-examined for mutations in their K2e genes.

Pityriasis amiantacea: a distinctive presentation of psoriasis associated with tumour necrosis factor-α inhibitor therapy.

Pityriasis amiantacea (PA; also known as tinea amiantacea) is a relatively rare but distinctive scalp condition characterized by thick scales that adhere to each other and to the hair shaft, resulting in agglomeration and matting of hair. Temporary alopecia is a common complication. Although a specific cause remains unclear, PA is associated with several inflammatory diseases such as psoriasis and seborrhoeic dermatitis. We present a case of PA as a complication of underlying psoriasis, which developed during tumour necrosis factor (TNF)-α inhibitor therapy for Crohn disease. This paradoxical cutaneous reaction to anti-TNF-α therapy has been recently described as an emerging and perplexing cause of psoriasis and psoriasiform eruptions.

The outcome of patients with nephrogenic systemic fibrosis after successful kidney transplantation.

Nephrogenic systemic fibrosis (NSF) is a debilitating disease in patients with severely diminished kidney function. Currently, no standard treatment exists but improvement has been reported after restoration of kidney function. We retrospectively studied 17 NSF patients with and without successful kidney transplantation (KTx) to evaluate the effects of KTx on NSF. Nine of the 11 KTx developed NSF pretransplant whereas two developed NSF immediately after KTx with delayed graft function. Two of the six dialysis patients had previous failed kidney transplants. Age and sex were well matched. All but one patient was dialysis dependent at the time of NSF. Median follow-up was 35 months for KTx patients and 9 months for dialysis patients. Kidney transplants achieved adequate renal function with median serum creatinine of 1.4 (0.9-2.8) mg/dL and a glomerular filtration rate of 42 (19-60) mL/min/1.73 m(2). NSF improved in 54.6% of the transplanted patients and 50% of the nontransplanted patients (p = 0.86). Two KTx patients had complete resolution of their symptoms whereas four had partial improvement. Improvement in the dialysis patients was all partial. Successful KTx did not insure improvement in NSF and in fact appeared to have no significant benefit over dialysis.

Activating BRAF mutations in eruptive melanocytic naevi.

BACKGROUND: Eruptive melanocytic naevi (EMN) are melanocytic proliferations developing rapidly on previously unaffected skin in association with various clinical scenarios, most commonly systemic immunosuppression. However, the exact mechanism leading to development of EMN is not understood. In particular, it is not known whether EMN harbour the BRAF mutations which occur frequently in melanoma and most common naevi. OBJECTIVES: To evaluate whether activating BRAF mutations may play a role in genesis of EMN. METHODS: Genomic DNA was isolated from 20 EMN from a patient treated with 6-mercaptopurine (6-MP). Primary BRAF genotyping was performed by allelespecific polymerase chain reaction, followed by validation using direct sequencing. RESULTS: The BRAF V600E mutation was identified in 85% of EMN examined. CONCLUSIONS: Our results implicate mutational activation of the BRAF­MAPK pathway as a factor in development of EMN in the setting of 6-MP treatment. The mechanism leading to development of EMN in this, and potentially other patients, may relate to synergistic mutagenic effects of thioguanines and ultraviolet (UV) A. Together with the documented importance of BRAF mutations in melanoma development and maintenance, these findings highlight the importance of UVA protection, especially in patients treated with thiopurines such as 6-MP.

Regulation of melanin biosynthesis in the human epidermis by tetrahydrobiopterin.

The participation of (6R) 5,6,7,8-tetrahydrobiopterin (6-BH4) in regulating the tyrosine supply for melanin biosynthesis was investigated by the examination of human keratinocytes, melanocytes, and epidermal suction blisters from normal human skin and from patients with the depigmentation disorder vitiligo. Cells, as well as total epidermis, contained high phenylalanine hydroxylase activities and also displayed the capacity to synthesize and recycle 6-BH4, the essential cofactor for this enzyme. In vitiligo, 4a-hydroxy-BH4 dehydratase activity was extremely low or absent, yielding an accumulation of the nonenzymatic by-product 7-tetrahydrobiopterin (7-BH4) at concentrations up to 8 x 10(-6) M in the epidermis. This by-product is a potent competitive inhibitor in the phenylalanine hydroxylase reaction with an inhibition constant of 10(-6) M. Thus, 6-BH4 seems to control melanin biosynthesis in the human epidermis, whereas 7-BH4 may initiate depigmentation in patients with vitiligo.