Reactive granulomatous dermatitis as a clinically relevant and unifying term: a retrospective review of clinical features, associated systemic diseases, histopathology and treatment for a series of 65 patients at Mayo Clinic.

BACKGROUND: Reactive granulomatous dermatitis (RGD) is an umbrella term used to describe interstitial granulomatous dermatitis (IGD), palisaded neutrophilic and granulomatous dermatitis (PNGD), and interstitial granulomatous drug eruption (IGDR). OBJECTIVE: The aim of this study was to describe systemic associations of RGD, explore possible associations between histopathologic findings and systemic RGD associations and determine clinical relevance of RGD subtypes. METHODS: We retrospectively studied clinical and histopathologic characteristics of patients with RGD from 1990 through 2020. RESULTS: Of 65 patients with RGD (41 women, 24 men; median age at diagnosis, 62 years), 37 had IGD, 26 had PNGD, and 2 had IGDR. Fifty patients (76.9%) had an associated systemic condition; rheumatologic conditions were identified for 34 (52.3%) patients. The associated systemic condition occurred before RGD in approximately 75% of patients. Statistical analyses did not show significant associations between specific subtypes of RGD and systemic diseases or treatment response, and specific histopathologic findings were not predictive of an associated systemic disease. CONCLUSIONS: Although most patients with RGD had an associated systemic condition, subtypes of RGD did not correlate with systemic associations, lending support to the use of the umbrella term RGD.

Preliminary method for profiling volatile organic compounds in breath that correlate with pulmonary function and other clinical traits of subjects diagnosed with cystic fibrosis: a pilot study.

Cystic fibrosis (CF) is characterized by chronic respiratory infections which progressively decrease lung function over time. Affected individuals experience episodes of intensified respiratory symptoms called pulmonary exacerbations (PEx), which in turn accelerate pulmonary function decline and decrease survival rate. An overarching challenge is that there is no standard classification for PEx, which results in treatments that are heterogeneous. Improving PEx classification and management is a significant research priority for people with CF. Previous studies have shown volatile organic compounds (VOCs) in exhaled breath can be used as biomarkers because they are products of metabolic pathways dysregulated by different diseases. To provide insights on PEx classification and other CF clinical factors, exhaled breath samples were collected from 18 subjects with CF, with some experiencing PEx and others serving as a baseline. Exhaled breath was collected in Tedlar bags during tidal breathing and cryotransferred to headspace vials for VOC analysis by solid phase microextraction coupled to gas chromatography-mass spectrometry. Statistical significance testing between quantitative and categorical clinical variables displayed percent-predicted forced expiratory volume in one second (FEV1pp) was decreased in subjects experiencing PEx. VOCs correlating with other clinical variables (body mass index, age, use of highly effective modulator treatment (HEMT), and the need for inhaled tobramycin) were also explored. Two volatile aldehydes (octanal and nonanal) were upregulated in patients not taking the HEMT. VOCs correlating to potential confounding variables were removed and then analyzed by regression for significant correlations with FEV1pp measurements. Interestingly, the VOC with the highest correlation with FEV1pp (3,7-dimethyldecane) also gave the lowestp-value when comparing subjects at baseline and during PEx. Other VOCs that were differentially expressed due to PEx that were identified in this study include durene, 2,4,4-trimethyl-1,3-pentanediol 1-isobutyrate and 5-methyltridecane. Receiver operator characteristic curves were developed and showed 3,7-dimethyldecane had higher ability to classify PEx (area under the curve (AUC) = 0.91) relative to FEV1pp values at collection (AUC = 0.83). However, normalized ΔFEV1pp values had the highest capability to distinguish PEx (AUC = 0.93). These results show that VOCs in exhaled breath may be a rich source of biomarkers for various clinical traits of CF, including PEx, that should be explored in larger sample cohorts and validation studies.

Serum triamcinolone levels during intensive, inpatient wet-dressing therapy.

BACKGROUND: Wet dressings combined with topical corticosteroids are beneficial for patients with generalized and refractory dermatosis; however, to our knowledge, serum levels after topical corticosteroid absorption during intensive therapy have not been reported previously. AIM: To examine serum levels of triamcinolone acetonide (TAC) after topical corticosteroid application during intensive wet-dressing therapy. METHODS: We performed a retrospective study of adult patients admitted for inpatient wet-dressing therapy from 7 November 2015 to 24 June 2016. Data were collected on sex, age, body surface area, TAC serum levels, number of wet-dressing changes after 24 and 48 h, and type of wet dressing. RESULTS: In total, 29 patients (14 men, 15 women) were assessed. Median [interquartile range (IQR)] age was 57 years (51.5-67.0 years) and involved body surface area was 1.98 m2 (1.88-2.15) m2 . Before the 24-hour blood draw, patients had received 1-3 dressing changes. Median (IQR) TAC level at 24 h was 0.33 µg/dL (0.20-0.58 µg/dL), with no significant difference noted between the number of dressing changes and TAC serum level. At 48 h, results of a serum TAC test were available for 22 patients with 2-6 dressing changes. Mean (IQR) serum level was 0.30 µg/dL (0.30-0.87 µg/dL). For each additional dressing change, there was an estimated 0.21 µg/dL increase in TAC serum level (95% CI 0.11-0.31; P < 0.001). TAC serum level was not significantly associated with sex, age, body surface area or dressing type. CONCLUSIONS: Intensive, inpatient wet-dressing therapy is associated with detectable TAC serum levels. However, we suspect that topical TAC has a primarily local therapeutic effect on the skin.

Treatment of acne with spironolactone: a retrospective review of 395 adult patients at Mayo Clinic, 2007-2017.

BACKGROUND: Few large studies have assessed spironolactone treatment of adult female acne. OBJECTIVES: To explore the role of spironolactone in the treatment of adult female acne. METHODS: We performed a retrospective case series assessing the efficacy of spironolactone treatment of a cohort of women evaluated at Mayo Clinic in Rochester, Minnesota, from 2007 through 2017. RESULTS: In total, 395 patients (median age, 32 years) received a median spironolactone dose of 100 mg daily. Approximately two-thirds of patients (66.1%) had a complete response; 85.1% had a complete response or a partial response greater than 50%. Median times to initial response and maximum response were 3 and 5 months. Efficacy was observed across all severity subtypes of acne, including those with papulopustular and nodulocystic acne. Patients received long-term treatment with spironolactone (median duration, 13 months) and had few adverse effects. CONCLUSIONS: Spironolactone is a safe and effective treatment of acne for women.

Topical sodium thiosulfate for calcinosis cutis associated with autoimmune connective tissue diseases: the Mayo Clinic experience, 2012-2017.

In this case series, we retrospectively identified all patients treated with topical sodium thiosulfate (TST) for calcinosis cutis (CC) associated with underlying autoimmune connective tissue diseases at Mayo Clinic (Rochester, MN, USA) during the period 1 January 2012 to 27 June 2017. Of 28 patients identified (mean age 57.0 years; 96% female), 19 (68%) had clinical improvement of their CC with TST, 7 (25%) had no response and 2 (7%) had unknown response. There were adverse events in three patients: two had skin irritation and the third, who had a zinc allergy, experienced pain with application. Overall, our findings support those of previous case reports that TST appears to be a relatively well-tolerated adjuvant treatment for CC, although future studies with a control group are warranted to assess the true efficacy of TST for the indication of CC.

Autoimmune myelofibrosis with pancytopenia as a presenting manifestation of systemic lupus erythematosus responsive to mycophenolate mofetil.

Hematological abnormalities, such as anemia, leucopenia, and thrombocytopenia, secondary to peripheral destruction, are common in systemic lupus erythematosus (SLE). However, cytopenias from autoimmune myelofibrosis (AIMF) are extremely uncommon in SLE, with less than 40 reported cases in the literature. We report the case of a 33-year-old female who presented with bullous skin lesions and pancytopenia as the presenting manifestation of what was ultimately diagnosed as SLE with AIMF. She responded well to glucocorticoids and mycophenolate mofetil.

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.

Plain radiography is effective for the detection of calcinosis cutis occurring in association with autoimmune connective tissue disease.

BACKGROUND: Studies on the radiological findings of calcinosis cutis in patients with autoimmune connective tissue disease (ACTD) are limited. OBJECTIVES: To describe imaging findings and radiological patterns of calcinosis cutis occurring with ACTD. METHODS: We retrospectively reviewed the cases of 37 patients with imaging studies assessing for calcinosis cutis associated with ACTD at our institution between 1996 and 2009. A formal blinded review of available images (i.e. radiographs, computed tomography scans) for all 37 patients was performed by radiologists. RESULTS: Of 37 patients, 30 (81%) were female. The mean age at diagnosis of calcinosis cutis was 43·4 years. Patients had the following ACTDs: dermatomyositis (n = 17) with classic (n = 9), juvenile (n = 7) and amyopathic (n = 1) subtypes; systemic sclerosis with limited cutaneous scleroderma (n = 8); undifferentiated connective tissue disease (n = 4); mixed connective tissue disease (n = 3); systemic lupus erythematosus (n = 2); lupus panniculitis (n = 1); overlap connective tissue disease (n = 1); and polymyositis (n = 1). Plain radiographs detected calcinosis in all 37 patients; a nodular pattern of calcification was most commonly observed (31/37; 84%). Two or more morphological patterns of calcification were present in 19 patients (51%). In general, individual patterns were not specific to a particular ACTD subtype. CONCLUSIONS: Radiography detected calcinosis in all patients and is recommended for initial imaging of calcinosis. Multiple morphological patterns of calcification were observed across ACTD subtypes. Further studies should correlate radiological studies with treatment of calcinosis and underlying ACTD.

Brachioradial pruritus: Mayo Clinic experience over the past decade.

BACKGROUND: Brachioradial pruritus (BRP) is a fascinating condition that is seen increasingly often, but any additional data from retrospective observational studies can still enhance our understanding. OBJECTIVES: To review our experience at the Mayo Clinic with patients presenting with BRP. METHODS: We retrospectively reviewed the clinical records of patients diagnosed with BRP between 1999 and 2011. RESULTS: In total, 111 patients (80 female, 72%) had been diagnosed with BRP. Their mean age was 59 years, range 12-84 years. Symptoms were bilateral in 84 (75.7%). Fifty-four patients (48.6%) reported prolonged exposure to the sun, and 16 had a history of neck concerns. Forty-five (40.5%) had undergone imaging studies of the neck; of these, eight had foraminal stenosis, six had protrusion of the intervertebral disk and six had stenosis of the spinal canal; 10 had more than one cervical abnormality. Thirty-one patients had been referred to neurology; eight of these had BRP attributed to a radiculopathy or peripheral neuropathy. Several topical and oral medications were prescribed. Seventy-five patients had a follow-up; of these, nine (12%) had complete resolution, 13 (17%) had improvement, four (5%) showed no change and 49 (65%) had no mention of BRP. CONCLUSIONS: Brachioradial pruritus presented most commonly in female patients and was observed over a wide age range. Although a third of patients with imaging studies had cervical abnormalities, the significance of these findings is unclear, as no structural causes of BRP were found in most cases. Some treatments were more successful than others.

Experience with the dermatology inpatient hospital service for adults: Mayo Clinic, 2000-2010.

BACKGROUND: There is a paucity of medical literature describing the role of dermatology inpatient hospital services for patients with severe dermatologic disease. A diminishing number of US hospitals have a dedicated dermatology inpatient service run by dermatologists. OBJECTIVES: To describe the role of a dermatology-run inpatient service in treatment of severe dermatologic disease from 2000 to 2010 at our institution. METHODS: We studied demographic characteristics, indications for admission and length of stay for the adult (age, >18 years) dermatology inpatient hospital service over the most recent decade. We compared data from the first 5.5 years with the subsequent 5.5 years and with previously published data. RESULTS: A total of 1732 patients had 2216 inpatient admissions to the adult service from 2000 to 2010. The mean (SD) age was 61.3 (17.7) years (age range 18-100 years). Median duration of admission was 3 days interquartile range (IQR), 2-5 days. The most common indications for admission were dermatitis (44.2%), psoriasis (17.4%) and cutaneous T-cell lymphoma (9.2%). We compared admissions from 2000 to mid-2005 (n = 1260) to admissions from mid-2005 to 2010 (n = 956). Statistically significant changes included median length of stay (decreased from 4 days [IQR, 3-6 days] to 3 days [IQR, 2-4 days] P < 0.01), admissions for psoriasis (decreased from 20.7% to 13.0%; P < .01) and admissions for dermatitis (increased from 41.6% to 47.6%; P < .01). CONCLUSION: The number of patients admitted and the median length of stay decreased between the 2 periods. Indications for admission have changed significantly across the two time periods.

Results of computer-assisted sensory evaluation in 41 patients with erythromelalgia.

BACKGROUND: Erythromelalgia is a rare disorder characterized by the clinical syndrome of burning pain, warmth and redness of the limbs. Neurological abnormalities (both large- and small-fibre neuropathy) are common. There have been few published reports on the sensory status of patients with erythromelalgia. AIM: To investigate the results of quantitative sensation testing in erythromelalgia using computer-assisted sensory evaluation, including vibratory detection threshold, cool detection threshold and heat-pain threshold (HPT). METHODS: Patients who underwent dermatological or neurological evaluation of suspected erythromelalgia at our institution and received a final diagnosis of erythromelalgia were identified from a master diagnosis index covering the period January 1994 to June 2008. A retrospective chart review was performed. Main outcome measures were sensory abnormalities (e.g. pain, burning sensation, tingling) in response to heat, cooling and vibration during computer-assisted sensory testing. RESULTS: In total, 41 patients with erythromelalgia were enrolled in the study and underwent computer-assisted sensory evaluation. Of these, 34 patients (82.9%) had abnormal results. The commonest abnormality was isolated HPT: 11 patients (26.8%) had heat hypoalgesia and 18 (43.9%) had heat hyperalgesia, whereas only 2 (4.9%) of the healthy control patients had hyperalgesia on testing. CONCLUSIONS: Multiple sensory modalities were found to be abnormal in patients with erythromelalgia, with the commonest clinical abnormality being isolated heat-pain abnormality. These findings lend support to the notion that neuropathy underlies the clinical diagnosis of erythromelalgia. Future studies will explore the nature of the relationship between these sensory abnormalities and the clinical features of erythromelalgia.

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.

Sustained moderate visual loss as a predictive end point for visual loss in non-proliferative diabetic retinopathy.

PURPOSE: In PKC-DRS2, the efficacy of the oral PKC-beta inhibitor, ruboxistaurin 32 mg/day, was measured by the primary end point of sustained moderate visual loss (SMVL: a > or = 15 letter decrease from baseline on the ETDRS (Early Treatment Diabetic Retinopathy Study) chart sustained at least for the last 6 months of study participation). We now evaluate whether SMVL is more accurate than moderate visual loss (MVL: a single occurrence of a decrease from baseline of > or = 15 ETDRS letters) for predicting future visual loss. METHODS: Study eyes with moderately severe to very-severe non-proliferative diabetic retinopathy, best-corrected visual acuity of at least 45 letters on the ETDRS chart (approximately Snellen 20/125), and no prior pan retinal photocoagulation were evaluated in 506 patients (869 eyes) who completed 36 months of treatment. RESULTS: Sixty-five percentage (26/40) of study eyes with the onset of SMVL within 24 months of enrolment still had SMVL at study completion (36 months). In comparison, only 24% (30/126) with MVL within 24 months had SMVL at study completion. Analyses based on data from 6, 12, and 18 months of treatment were similar. CONCLUSIONS: SMVL is a more predictable measure of subsequent visual loss than is a single time point measure of MVL.

Incidence of erythromelalgia: a population-based study in Olmsted County, Minnesota.

OBJECTIVE: To estimate the population-based incidence of erythromelalgia. Background Only one report describing the incidence of erythromelalgia has been published previously. STUDY DESIGN: A population-based analysis of data from the Rochester Epidemiology Project. SETTING: Tertiary care medical centre in Olmsted County, Minnesota (a rural county in the south-eastern portion of the state). PATIENTS: Thirty-three residents of Olmsted County with a diagnosis of erythromelalgia during the study period. METHODS: Age- and sex-specific incidence rates of erythromelalgia were determined. INTERVENTION: None. MAIN OUTCOME: Population-based incidence rate. RESULTS: The overall age- and sex-adjusted incidence rate (95% confidence interval, 95% CI) was 1.3 (0.8-1.7) per 100,000 people per year. The incidence of primary and secondary erythromelalgia was 1.1 (0.7-1.5) and 0.2 (0.02-0.4) per 100,000 people per year, respectively. The age-adjusted incidence rates (95% CI) were 2.0 (1.2-2.7) per 100,000 women and 0.6 (0.1-1.1) per 100,000 men. The study was limited by the small sample size and potential variability in recognition of erythromelalgia. CONCLUSION: The population-based incidence of erythromelalgia has increased with each decade in Olmsted County over the past three decades; overall incidence was 1.3 per 100,000 people per year, approximately 5 times higher than previously reported.