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.

Clinical and histopathological features of adult patients with dermatomyositis and melanoma differentiation associated-5 autoantibody seropositivity status, as determined by commercially available testing: a retrospective, single-institution comparative cohort study.

BACKGROUND: Although melanoma differentiation associated (MDA)-5 autoantibodies have been widely explored in dermatomyositis (DM), most studies have relied on MDA-5 autoantibody testing performed in research settings, rather than the now-available commercial laboratory tests. AIM: To characterize the clinical and histopathological data in patients with DM and circulating MDA-5 autoantibodies, as defined by commercially available testing. METHODS: This was a retrospective review of patients with DM who underwent MDA-5 antibody testing. All available skin biopsy slides were reviewed. RESULTS: Cutaneous features more prevalent in MDA-5-positive DM included Raynaud phenomenon (RP) (P < 0.001), cutaneous ulcerations (P = 0.01), mechanic hands (P < 0.02), palmar papules (P < 0.01), oral ulcers (P = 0.024) and alopecia (P = 0.03). Joint and pulmonary involvement were more common in patients with MDA-5-positive DM (both P < 0.001) as was dysphagia (P < 0.01). Myopathy (P = 0.4) and malignancy (P = 0.34) were not statistically different between the cohorts. Vasculopathy was more common in MDA-5-positive DM (P < 0.01), while spongiosis was less common (P < 0.02). CONCLUSION: This study not only confirms some known associations between disease manifestations and MDA-5 autoantibody status, as determined by commercially available tests, but also identifies new associations, including RP and dysphagia.

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.

Leukocytoclastic vasculitis in children: clinical characteristics, subtypes, causes and direct immunofluorescence findings of 56 biopsy-confirmed cases.

BACKGROUND: Leukocytoclastic vasculitis (LCV) in children is a complex group of conditions. OBJECTIVES: This study presents the demographics, clinical features, direct immunofluorescence (DIF) results and suspected aetiologies of 56 biopsy-confirmed cases of leukocytoclastic vasculitis in children. METHODS: Retrospective review of 56 children seen at Mayo Clinic in Rochester, Minnesota, from 1993 to 2013 with clinical features and cutaneous biopsy consistent with LCV. RESULTS: Twenty-seven (48%) cases were found to be due to IgA vasculitis (Henoch-Schonlein purpura). The remaining cases were found to be due to cutaneous small-vessel vasculitis (n = 19, 34%), urticarial vasculitis (n = 5, 9%), ANCA-associated vasculitis (n = 4, 7%) and acute haemorrhagic oedema of infancy (n = 1, 2%). IgA vasculitis was found to be associated with abdominal pain (P = 0.008), whereas the non-IgA vasculitis group was associated with headache (P = 0.052). Children with IgA vasculitis had palpable purpura (P = <0.001), petechia (P = 0.057), vesicles (P = 0.009) and involvement of the buttock (P = 0.004) more frequently than the non-IgA vasculitis group. On DIF, perivascular IgA was positive in IgA vasculitis compared to non-IgA vasculitis cases (P = <0.001), the other conjugates were similar between the two groups. CONCLUSION: The most common subtype of biopsy-confirmed LCV in children is IgA vasculitis. Clinical features, exam characteristics and DIF results can be helpful in determining the subtype of cutaneous vasculitis in children.

Periodontitis and risk of psoriasis: a systematic review and meta-analysis.

BACKGROUND: The association between periodontitis and systemic diseases has been increasingly recognized. However, the data on the association between periodontitis and psoriasis are still limited. OBJECTIVES: To summarize all available data on the association between periodontitis and the risk of psoriasis. METHODS: Two investigators independently searched published studies indexed in MEDLINE and EMBASE databases from inception to July 2016 using a search strategy that included terms for psoriasis and periodontitis. Studies were included if the following criteria were met: (i) case-control or cohort study comparing the risk of psoriasis in subjects with and without periodontitis; (ii) subjects without periodontitis were used as comparators in cohort studies while participants without psoriasis were used as controls in case-control studies; and (iii) effect estimates and 95% confidence intervals (CI) were provided. Point estimates and standard errors from each study were extracted and combined together using the generic inverse variance technique described by DerSimonian and Laird. RESULTS: Two cohort studies and three case-control studies met the inclusion criteria and were included in the meta-analysis. The pooled risk ratio of psoriasis in patients with periodontitis versus comparators was 1.55 (95% CI, 1.35-1.77). The statistical heterogeneity was insignificant with an I2 of 18%. Subgroup analysis according to study design revealed a significantly higher risk among patients with periodontitis with a pooled RR of 1.50 (95% CI, 1.37-1.64) for cohort studies and a pooled RR of 2.33 (95% CI, 1.51-3.60) for case-control studies. CONCLUSIONS: Patients with periodontitis have a significantly elevated risk of psoriasis.

Epidemiology of cutaneous sarcoidosis, 1976-2013: a population-based study from Olmsted County, Minnesota.

BACKGROUND: The epidemiology of cutaneous sarcoidosis is not well-characterized as only referral-based studies are available. OBJECTIVES: To characterize the epidemiology of cutaneous sarcoidosis, with emphasis on annual incidence and clinical characteristics, from 1976 to 2013. METHODS: Inception cohorts of patients with incident isolated cutaneous sarcoidosis and incident systemic sarcoidosis with cutaneous involvement in 1976-2013 in Olmsted County, Minnesota, United States were identified based on comprehensive individual medical record review. Inclusion in the isolated cutaneous sarcoidosis cohort required physician diagnosis and skin biopsy showing non-necrotizing granuloma. Inclusion in the systemic sarcoidosis with cutaneous involvement cohort required presence of systemic sarcoidosis and cutaneous lesions. Presence of systemic sarcoidosis was determined by physician diagnosis supported by histopathology of non-necrotizing granuloma, characteristic radiologic features of intrathoracic sarcoidosis and exclusion of other granulomatous diseases. Cutaneous lesions were defined as either sarcoidosis-specific or non-specific. RESULTS: There were 62 cases with sarcoidosis-specific cutaneous lesions (36 cases of sarcoidosis-specific cutaneous lesions and 26 cases of isolated cutaneous sarcoidosis) which corresponded to an incidence of 1.9 per 100 000 population. The female to male ratio was 2.1 : 1. Plaques, papules and subcutaneous nodules were the most commonly observed cutaneous lesions. There was no significant difference in cutaneous presentation between those who had isolated skin disease and those who had skin disease in association with systemic sarcoidosis. Prognosis of cutaneous sarcoidosis was favourable, as over 90% of patients had a good response to either glucocorticoids, hydroxychloroquine or tetracycline antibiotics. This study has a significant limitation, in that the studied population was predominantly Caucasians who generally have a lower prevalence of skin disease. CONCLUSIONS: The incidence of sarcoidosis-specific cutaneous lesions was about 1.9 per 100 000 population with female predominance. The cutaneous presentations were similar among those with and without systemic sarcoidosis.

Henoch-Schönlein purpura and systemic disease in children: retrospective study of clinical findings, histopathology and direct immunofluorescence in 34 paediatric patients.

BACKGROUND: Henoch-Schönlein purpura (HSP), an IgA-mediated small vessel vasculitis, is the most common form of vasculitis in children. HSP is commonly associated with systemic involvement of the gastrointestinal tract, joints and kidneys. Renal involvement is the main cause of morbidity and mortality in HSP. OBJECTIVES: To characterize the clinical, histopathological and direct immunofluorescence (DIF) findings, and to correlate the findings with systemic disease in 34 children with HSP seen at our institution. METHODS: This was a retrospective review of paediatric patients with HSP and with available biopsy specimens seen at our institution between 1993 and 2013. RESULTS: Thirty-four paediatric patients were identified (mean age 10·7 years). Renal involvement was found in 17 (50%) patients, gastrointestinal tract involvement in 22 (65%) and joint involvement in 23 (68%). Renal involvement was significantly associated with papillary dermal oedema on histopathology (P < 0·01) and the presence of perivascular C3 on DIF (P = 0·01). The presence of lesions above the waist was significantly associated with gastrointestinal involvement (P = 0·03), as was the presence of clinically apparent oedema (P = 0·01). CONCLUSIONS: This study suggests that in children with HSP, microscopic dermal oedema and C3 on DIF may be predictive of renal involvement. Patients with clinically apparent oedema and lesions above the waist are more likely to have gastrointestinal involvement.

Evidence-based guidelines for laboratory screening for infectious diseases before initiation of systemic immunosuppressive agents in patients with autoimmune bullous dermatoses.

Autoimmune bullous dermatoses (ABD) compromise the skin's innate barrier function for preventing infection. Treating patients with ABD frequently requires systemic immunosuppressive therapy, often with multiple agents. Currently, no pretreatment infection testing guidelines are available for clinicians caring for patients with ABD. We performed a systematic literature review in other medical disciplines that use similar iatrogenic immunosuppressive medications to treat various diseases and conditions and developed infection-testing recommendations for patients with ABD before initiating immunosuppressive therapy. Assessing individual patient risk factors for latent infection and preventable communicable diseases can direct testing for select infections before starting immunosuppressive therapy. Testing patients for hepatitis B virus, hepatitis C virus, and Mycobacterium tuberculosis infection is recommended before initiating rituximab treatment.

Histopathological findings in cutaneous small-vessel vasculitis associated with solid-organ malignancy.

BACKGROUND: Histopathological findings in biopsy specimens from patients with cutaneous small-vessel vasculitis (CSVV) secondary to solid-organ malignancy have not been previously reported. OBJECTIVES: We aimed to understand better the differences in histopathological findings between biopsy specimens from patients with CSVV associated with solid-organ malignancies and patients with CSVV secondary to other causes. METHODS: From a previously published group of patients with CSVV and solid-organ malignancy, we identified patients with available histopathology slides of biopsy specimens. We compared histopathological findings from these patients with those from 68 previously published patients with Henoch-Schönlein purpura not associated with solid-organ malignancy (60% male). RESULTS: We identified 15 patients (eight male, 53%) with available slides from biopsy specimens. The mean age of these patients with solid-organ malignancy-associated CSVV was 66·6 years, compared with 45·8 years in the Henoch-Schönlein purpura cases not associated with solid-organ malignancy (P < 0·001). Solid-organ malignancy-associated CSVV was less likely to demonstrate papillary dermal oedema (P = 0·04), papillary dermal inflammation (P < 0·001) and lymphocytes (P < 0·001), and more likely to have plasma cells (P = 0·02). Additionally, we detected nonsignificant differences in the presence of histiocytes (P = 0·05), intravascular thrombosis (P = 0·052) and microabscess formation (P = 0·06). CONCLUSIONS: CSVV associated with solid-organ malignancies tended to have deeper dermal involvement and a different cellular milieu from cases not associated with solid-organ malignancies. In addition, the patients with CSVV with solid-organ malignancies were significantly older than those without. Prospective studies with age-matched controls are needed to determine the clinical significance of the histopathological differences in solid-organ malignancy-associated CSVV.

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.

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.

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.