Treatment of morphea with hydroxychloroquine: A retrospective review of 84 patients at Mayo Clinic, 1996-2013.

BACKGROUND: Few studies support treating morphea (localized scleroderma) with hydroxychloroquine. OBJECTIVE: To assess the efficacy of hydroxychloroquine treatment of morphea. METHODS: We conducted a retrospective study of 84 patients who had morphea and were treated with hydroxychloroquine monotherapy for at least 6 months at our institution from 1996 through 2013. The median times to initial and maximal responses were assessed. RESULTS: Of the 84 patients (median age at diagnosis, 29.5 years), 65 (77.4%) were female, 36 (42.9%) had a complete response to hydroxychloroquine, 32 (38.1%) had a partial response greater than 50%, 10 (11.9%) had a partial response less than or equal to 50%, and 6 (7.1%) had no response. The median time to initial response was 4 months, and the median time to maximal response was 12 months. Ten patients (11.9%) experienced adverse effects from hydroxychloroquine; the most common adverse effect was nausea (6 patients). LIMITATIONS: Retrospective study. CONCLUSIONS: Hydroxychloroquine is a valuable treatment for morphea because of its high response rate and low rate of adverse effects; however, prospective studies are needed to determine its true efficacy.

Dermatologic manifestations of solid organ transplantation-associated graft-versus-host disease: A systematic review.

BACKGROUND: Graft-versus-host-disease (GVHD) after solid organ transplantation (SOT) is extremely rare. OBJECTIVE: To investigate the dermatologic manifestations and clinical outcomes of SOT GVHD. METHODS: Systematic literature review of SOT GVHD. RESULTS: After full-text article review, we included 61 articles, representing 115 patients and 126 transplanted organs. The most commonly transplanted organ was the liver (n = 81). Among 115 patients, 101 (87.8%) developed skin involvement. The eruption appeared an average of 48.3 days (range, 3-243 days) posttransplant and was pruritic in 5 of 101 (4.9%) cases. The eruption was described as morbilliform in 2 patients (1.9%), confluent in 6 (5.9%), and desquamative in 4 (3.9%) cases. In many cases, specific dermatologic descriptions were lacking. The mortality rate was 72.2%. Relative time of death was reported in 23 patients who died during the follow-up period. These patients died an average of 99.2 days (range, 22-270 days) posttransplant, or 50.9 days after the appearance of dermatologic symptoms. Frequent causes of death were sepsis and multiorgan failure. LIMITATIONS: Incomplete descriptions of skin findings and potential publication bias resulting in publication of only the most severe cases. CONCLUSIONS: GVHD is a potentially fatal condition that can occur after SOT and often presents with a skin rash. We recommend that dermatologists have a low threshold to consider and pursue this diagnosis in the setting of post-SOT skin eruption.

Clinical and histopathologic manifestations of solid organ transplantation-associated graft-versus-host disease involving the skin: A single-center retrospective study.

BACKGROUND: Graft-versus-host disease (GVHD) following solid organ transplantation (SOT) is extremely rare and infrequently described in the dermatologic literature. METHODS: We performed a retrospective clinicopathologic review of our institution's experience with patients diagnosed with SOT-associated GVHD (SOT GVHD) (May 1, 1996 to September 1, 2017). RESULTS: Of nine patients with SOT GVHD, seven had undergone liver transplantation, while two had undergone lung transplantation. All presented initially with a skin eruption, which developed an average of 63 days (range: 11-162 days) post transplant. The average time to diagnosis following the onset of the skin eruption was 12 days (range: 0-54 days). Diagnosis was often delayed because of a competing diagnosis of drug reaction. Frequent skin findings included pruritic erythematous to violaceous macules and papules with desquamation. Histopathology showed vacuolar interface dermatitis in 12 of 15 cases (80.0%). Of the 11 specimens in which a hair follicle was present for evaluation, vacuolar interface changes around the hair follicle were present in eight (72.7%) cases. Seven patients (77.8%) died from complications during the follow-up period. CONCLUSIONS: SOT GVHD presents initially with skin involvement, is associated with vacuolar interface changes on skin biopsy, and is associated with a high mortality rate. Clinicopathologic correlation is required for accurate diagnosis.

Prevalence of allergen sensitization detected by patch tests.

BACKGROUND: Existing literature on the prevalence of positive reactions to allergens is largely derived from dermatologists who practice at large academic centers. Data from other providers, including allergists who practice in various other settings, is important to assess a more representative and accurate prevalence of contact allergy. OBJECTIVE: To determine the prevalence of contact allergy among individuals with at least one positive patch test result by comparing data for positive patch test reaction rates of common contact allergens from 3 groups based in different practice settings, 2 of which are academic. METHODS: We retrospectively analyzed patch test results of an academic center (January 1, 2011, to December 4, 2015) and a national contact allergen database (March 1, 2015, to September 1, 2016). Data from a third, academic-based group was obtained separately from the published literature. Logistic regression analysis was used to compare positive reaction rates of the widely available, patch test allergens among the 3 groups. RESULTS: The positive reaction rates for 10 of 36 compared allergens (28%) were significantly higher (p < 0.05) for the national contact allergen database compared with both the academic groups. CONCLUSION: Positive reaction rates to common allergens used in patch testing may be underreported in the literature. Limitations of our study included the retrospective nature of the study, different date ranges among the three groups, and the absence of all allergens tested by the national contact allergen database.

Histopathology of Calciphylaxis: Cohort Study With Clinical Correlations.

Calciphylaxis is a rare, painful, and life-threatening condition with a high mortality rate. Although the etiology of calciphylaxis is not well understood, it has been proposed that calcium deposition within and around subcutaneous vessels restricts blood flow chronically, thereby predisposing the patient to acute pannicular and dermal thrombosis. Given increasing recognition of the role of hypercoagulability in calciphylaxis, this retrospective cohort study sought to evaluate the presence of thromboses and dermal angioplasia in calciphylaxis. Moreover, we aimed to validate previous observations about the histopathology of calciphylaxis compared with skin biopsies from patients with end-stage renal disease but without calciphylaxis. After a meticulous clinical chart review, we assessed the corresponding skin biopsies for the presence of vessel calcification, thromboses, and dermal angioplasia in skin biopsies from patients with calciphylaxis (n = 57) and compared with those from patients with end-stage renal disease but without calciphylaxis (n = 26). Histopathologic findings were correlated with clinical features such as chronic kidney disease, diabetes, or associated malignancy. Our results validated a prior observation that calciphylaxis was significantly more likely to show calcification of dermal vessels and diffuse dermal thrombi. This study reports the frequent finding of dermal angioplasia, a potential marker of chronic low-grade ischemia, as another frequent microscopic finding in calciphylaxis. Among cases of calciphylaxis, histopathologic changes in patients with chronic kidney disease were indistinguishable from those in patients without chronic kidney disease, thereby implying a final common pathogenic pathway in both uremic and nonuremic calciphylaxis. In future, larger, prospective studies may be useful in validating these findings.

Clinical features, causes, treatments, and outcomes of peristomal pyoderma gangrenosum (PPG) in 44 patients: The Mayo Clinic experience, 1996 through 2013.

BACKGROUND: There are limited large case series of peristomal pyoderma gangrenosum (PPG), an uncommon cause of recalcitrant peristomal ulceration. OBJECTIVE: We sought to further characterize the clinical features, causes, treatments, and outcomes of PPG. METHODS: We conducted a retrospective chart review of patients with PPG seen at Mayo Clinic from January 1996 to July 2013. RESULTS: A total of 44 patients had PPG (mean age, 46 years; 32 women [73%]); 41 (93%) had inflammatory bowel disease. Mean time to PPG onset after stoma surgery was 5.2 months (excluding 1 outlier). Systemic therapies included corticosteroids (66%), immunosuppressants (41%), biologics (36%), and a combination of systemic treatments (36%). Mean time to reach a complete response was 10.7 weeks. Stoma closure had the greatest complete response (4 of 4 patients, no recurrences). Recurrence after any treatment was documented in 23 of 38 (61%) patients. Stoma relocation/revision recurred in 10 of 15 (67%) patients. Remission occurred in 29 of 31 (94%) patients. LIMITATIONS: Small sample size and retrospective study design are limitations. CONCLUSION: PPG is strongly associated with inflammatory bowel disease, is predominant in women, and has a prolonged time to onset and high recurrence rate. Systemic corticosteroid or combination therapies and surgical closure can be effective treatments. Timely recognition and management are paramount to achieving early remission.

Kaposi varicelliform eruption in patients with Darier disease: a 20-year retrospective study.

BACKGROUND: Kaposi varicelliform eruption (KVE), or herpes simplex virus (HSV) superinfection of pre-existing skin lesions, may complicate Darier disease. OBJECTIVE: We sought to compare the clinical features and outcomes of patients with Darier disease who developed KVE superinfection with those who did not. METHODS: A 20-year retrospective analysis of 79 patients with Darier disease treated at our institution was performed. RESULTS: Eleven (14%) patients developed KVE, of whom 45% required hospitalization for their skin disease during the follow-up period. Patients with KVE had more severe Darier disease (P = .030) and were more likely to be hospitalized (P = .015). HSV was detected in erosions without concomitant vesicles or pustules in 64% of confirmed cases. In all, 23 (55%) patients with erosions had HSV testing pursued. LIMITATIONS: Retrospective study design is a limitation. CONCLUSION: The majority of KVE occurs in painless or painful erosions that may also appear impetiginized without vesicle or pustule formation. As HSV superinfection is correlated with severe Darier disease and risk for hospitalization, increased recognition of this phenomenon may lead to better patient outcomes.

Cutaneous microemboli from hydrophilic polymer after endovascular procedures.

BACKGROUND: Multiple devices and coatings assist with endovascular insertion of sheaths, catheters, and guide wires. Hydrophilic polymer coatings, a common component of endovascular surgical devices, reportedly cause microvascular obstruction and embolization, with various sequelae in organs and soft tissue. OBJECTIVE: We sought to describe clinical and histopathologic features of cutaneous manifestations of hydrophilic polymer gel emboli. METHODS: We evaluated the clinical and histopathologic characteristics of 8 patients with cutaneous complications of hydrophilic polymer gel emboli who presented in May 2013 through February 2015. RESULTS: Sudden onset of lower extremity livedo racemosa, purpuric patches, or both, occurred hours to days after endovascular procedures involving the aorta. Histopathologic evaluation showed basophilic lamellated material, consistent with hydrophilic polymer gel emboli, within small dermal vessels. LIMITATIONS: This was a retrospective study with small sample size and not controlled for all similar procedures in this population. CONCLUSION: Hydrophilic polymer gel coatings in endovascular devices can embolize to skin and cause microvascular occlusion, presenting as livedo racemosa, purpura, or both. Given the number of patients observed over a short period, this phenomenon may be underappreciated. Hydrophilic polymer gel emboli should be considered in differential diagnosis of livedo racemosa and purpura after endovascular procedure.

Postoperative pyoderma gangrenosum (PG): the Mayo Clinic experience of 20 years from 1994 through 2014.

BACKGROUND: Postoperative pyoderma gangrenosum (PG) is a neutrophilic dermatosis characterized by the development of PG-type lesions within surgical sites. OBJECTIVE: We sought to characterize postoperative PG as a distinct subtype of PG for earlier recognition and prevention of improper therapy. METHODS: We conducted a retrospective chart review of patients with nonperistomal postoperative PG at Mayo Clinic from 1994 to 2014.x RESULTS: Eighteen patients had postoperative PG with an average age of 58 years. Fifteen (83%) were female. Among patients with postoperative PG, 4 (22%) had an associated systemic disease traditionally associated with PG. Sites of postoperative PG included 7 breast (38%), 7 abdomen (38%), 1 back, 1 shoulder, 1 ankle, and 1 scrotum, witxxh breast reconstruction being the most common surgery. The average time to symptoms was 11 days. No patients had a fever. Eight (44%) had documented anemia and 5 (27%) had leukocytosis. Antibiotics and systemic corticosteroids were initiated in 10 (56%) and 14 (83%), respectively. Debridement was done in 11 (61%) patients. LIMITATIONS: Small sample size and retrospective study are limitations. CONCLUSION: Postoperative PG is a rare surgical complication with predilection for the breast and abdomen of females and has less association with systemic disease than idiopathic PG. Early recognition may prevent unnecessary debridements and morbidity.

Acute cutaneous graft-vs.-host disease compared to drug hypersensitivity reaction with vacuolar interface changes: a blinded study of microscopic and immunohistochemical features.

BACKGROUND: Complications from graft-vs.-host disease (GVHD), a major contributor to morbidity and mortality following hematopoietic cell transplantation, may be mitigated by early diagnosis and intervention. However, differentiation between acute cutaneous GVHD and other common skin eruptions that develop in the post-transplantation period, such as drug hypersensitivity reaction, can be challenging clinically and microscopically. Because recent evidence indicates that CD123, a marker of plasmacytoid dendritic cells, can help to distinguish gastrointestinal GVHD from the clinicopathologic mimic cytomegalovirus colitis, we aimed to determine whether CD123 could aid in the diagnosis of acute cutaneous GVHD. METHODS: We studied 12 skin specimens of patients with grades I-II cutaneous GVHD and 12 from patients who had drug hypersensitivity reaction with vacuolar interface changes on biopsy. RESULTS: No differences were seen between the two groups with regards to density or distribution of CD123 expression. Specimens representing GVHD showed significantly less spongiosis (P < 0.001) and fewer dermal eosinophils (P = 0.03) compared to those representing drug hypersensitivity reaction. CONCLUSIONS: We conclude that CD123 does not appear to be a useful ancillary test in the diagnosis of acute cutaneous GVHD. Careful correlation between clinical findings and features with microscopy remains the cornerstone of accurate diagnosis of acute cutaneous GVHD.

Therapeutic dose monitoring of mycophenolate mofetil in dermatologic diseases.

BACKGROUND: Mycophenolate mofetil (MMF) is used for prevention of allograft rejection in transplantation medicine. In dermatology it is used as a corticosteroid-sparing agent. The pharmacokinetics of MMF are known to vary by individual. Therapeutic dose monitoring of mycophenolic acid (MPA), the active metabolite of MMF, is used as a guide in transplantation medicine, but limited data exist on the benefit of measuring MPA levels in the management of dermatologic disease. OBJECTIVE: We sought to describe the use of MPA level monitoring in the management of dermatologic disease. METHODS: We retrospectively searched for cases of patients who were treated with MMF for a dermatologic condition at our tertiary care center, and who had at least 1 trough level measurement of MPA from January 1, 2003, through November 30, 2009. RESULTS: Our search identified 24 patients treated with MMF for autoimmune bullous diseases, connective tissue diseases, erythema multiforme, atopic dermatitis, or pyoderma gangrenosum who had at least 1 MPA trough level measured. The range of MPA levels in patients who responded to therapy was 1.2 to 8 µg/mL at a dose range of 1 to 3.5 g/d of MMF. Four cases were analyzed in detail to highlight the use of therapeutic dose monitoring in the management of dermatologic disease. LIMITATIONS: This was a retrospective study. CONCLUSION: We recommend monitoring MPA levels only in patients not responding to the standard 2-g/d dosage of MMF. MPA levels can help the dermatologist to increase the dose in patients who have poor absorption or to detect therapeutic noncompliance.

Pediatric hospital dermatology: experience with inpatient and consult services at the Mayo Clinic.

Data describing the management of pediatric patients admitted to a hospital under the care of a dermatologist and dermatology hospital consults for pediatric inpatients are limited. We aim to describe the role of an inpatient hospital service jointly run by dermatology and pediatrics and the activities of a pediatric dermatology hospital consult service. We retrospectively identified pediatric (age < 18 yrs) dermatology inpatients and hospital consult patients from January 1, 2009, through December 31, 2010. We examined patient demographics, indications for admission, length of stay, treatment provided, consult-requesting service, and consult diagnosis. One hundred eight admissions were by a dermatologist. The mean age was 5.8 years; the median length of stay was 3 days. Indications for admission included atopic dermatitis (86.1%), psoriasis (3.7%), and eczema herpeticum (2.8%). The main treatment provided was wet dressings (97.2%). Eighty-three dermatology hospital consults were requested. The mean age was 7.4 years. The main indications for dermatology consultation included drug rash (12.1%), cutaneous infections (12.1%), contact dermatitis (9.6%), psoriasis (8.4%), atopic dermatitis (6.0%), and hemangiomas (6.0%). This study describes the utility of the hospital pediatric dermatology inpatient and consult services in treating patients with severe skin disease.

In search of prognostic indicators for lymphomatoid papulosis: a retrospective study of 123 patients.

BACKGROUND: Lymphomatoid papulosis (LyP) is a benign recurrent papulonodular skin eruption with histologically malignant features that sometimes (10%-20%) progresses to lymphoma. OBJECTIVE: We retrospectively evaluated the clinical course of patients with LyP and identify prognostic factors possibly indicating a malignant course. METHODS: Clinical, histopathologic, and immunologic features and molecular genetics were examined and correlated with clinical course and outcomes. Immunophenotyping and chemokine profiling were performed in select skin biopsy samples. A follow-up questionnaire was sent to patients. Clinical course and association with neoplastic disorders were correlated with LyP subtypes, molecular genetics, and immunophenotyping studies. RESULTS: Of 123 patients with LyP (1991-2008) followed up a mean of 4 years (range, 2 months to 14 years), 17 (14%) had an associated hematologic malignancy, 8 of which were mycosis fungoides. Histopathologic analyses demonstrated classic LyP type A (n = 69), B (n = 13), or C (n = 6), and a slight predominance of T-cell CD8 marker expression for type A. More than one type of lesion was present in 9 patients with a higher incidence of hematologic malignancies. T-cell receptor gene rearrangement positivity was about two times higher, with LyP associated with hematologic malignancy (82% vs 44%; odds ratio 5.7; P = .02). Chemokine studies in a subset of 25 patients showed chemokine receptor (CCR) CCR4(+) and thymus and activation-related chemokine (TARC(+)) in all LyP types and CCR3(+) and chemokine-related receptor (CXCR) CXCR3(+) in types B and C. LIMITATIONS: Retrospective study design is a limitation. CONCLUSIONS: Positive T-cell receptor gene rearrangement or diagnosis of mixed-type LyP may be a prognostic indicator of disease more prone to progress to lymphoma.

Wet dressing therapy in conjunction with topical corticosteroids is effective for rapid control of severe pediatric atopic dermatitis: experience with 218 patients over 30 years at Mayo Clinic.

BACKGROUND: At our institution, hospitalization for intensive treatment (combining wet dressings and topical corticosteroids) is a primary intervention for severe pediatric atopic dermatitis. Prior reports of this treatment are limited. OBJECTIVE: We sought to review the efficacy of wet dressings for pediatric atopic dermatitis. METHODS: We reviewed records of pediatric patients hospitalized from January 1, 1980, through April 20, 2010, who received intensive topical treatments for atopic dermatitis. RESULTS: In total, 218 pediatric patients had widespread atopic dermatitis severe enough to warrant hospitalization, despite prior outpatient topical treatments and other interventions such as immunomodulating agents, phototherapy, dietary manipulation, or contact allergen avoidance. Mean (SD) age was 5.97 (4.91) years (range, 2 months-17 years); 141 patients (65%) were female. There were 266 hospitalizations: 192 patients (72%) had one admission, 15 (6%) had two admissions, and 11 (4%) had 3 or more admissions. Mean (SD) duration of hospitalization was 3.61 (2.23) days (range, 1-16 days). Upon discharge, all patients showed improvement. In 239 of 266 hospitalizations, patient records showed quantification of improvement (global assessment): 121 (45%) had 75% to 100% improvement, 102 (38%) had 50% to 75% improvement, and 16 (6%) had 25% to 50% improvement. LIMITATIONS: This was a retrospective study. CONCLUSION: Intensive inpatient treatment (with wet dressings and topical corticosteroids) was highly effective in controlling severe and recalcitrant atopic dermatitis. Intensive topical treatment, although underused, is an effective first-line approach for patients with severe atopic dermatitis.

Palliative care utilization in calciphylaxis: a single-center retrospective review of 121 patients (1999-2016).

BACKGROUND: Calciphylaxis is a debilitating dermatological condition associated with high rates of morbidity and mortality. Palliative care offers a multidisciplinary approach to addressing symptoms and goals of care in patients with serious medical diagnoses. Involvement of palliative services for calciphylaxis is infrequently reported in the literature. The purpose of this report is to assess rates of palliative and pain consultation for patients with calciphylaxis. METHODS: This is a comprehensive, single-institution retrospective chart review of 121 eligible patients with a diagnosis of calciphylaxis treated at Mayo Clinic in Rochester, Minnesota, from 1999 to 2016. Inclusion criteria were an indisputable diagnosis of calciphylaxis based on clinical, histopathologic, and radiographic features. One hundred twenty-one patients met inclusion criteria. RESULTS: Fifty-one patients (42%) received either a palliative (n = 15) or pain (n = 20) consultation, or both (n = 16). Patients with a palliative care consultation were younger compared with those without (mean ages 57 vs. 62 years, P = 0.046). In 104 patients (86%), psychiatric symptoms were not assessed. CONCLUSIONS: In this cohort of patients with calciphylaxis, the majority do not receive palliative and pain care consultations. Psychiatric complications are inconsistently addressed. These observations highlight practice gaps in the care of patients with calciphylaxis.

Relapsed hepatosplenic T-cell lymphoma heralded by a solitary skin nodule.

Hepatosplenic T-cell lymphoma (HSTL) represents a rare form of peripheral T-cell lymphoma composed of lymphocytes that typically express the γδ T-cell receptor. This form of lymphoma rarely involves the skin. We report the case of a 23-year-old man with a history of HSTL that was presumed to be in remission who presented with a solitary cutaneous nodule. Skin biopsy showed an atypical lymphocytic infiltrate arranged in a perivascular and periappendageal pattern with associated vacuolar epidermal interface change. The constituent T cells expressed CD2, CD3, CD7, CD8, ß-F1, γδ T-cell receptor, Tia-1 and granzyme B. The cells lacked the expression of CD4, CD5 and CD56. Fluorescence in situ hybridization (FISH) showed a characteristic chromosomal abnormality, namely isochromosome 7q, which confirmed the diagnosis of cutaneous HSTL. On restaging his disease, widespread progression was noted. To our knowledge, this report provides the first detailed account of cutaneous involvement by HSTL. We show the novel utility of FISH to identify isochromosome 7q in the lesional skin of HSTL patients.

Differences between Stevens-Johnson syndrome versus toxic epidermal necrolysis.

BACKGROUND: To retrospectively review the outcomes of two rare cutaneous diseases, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and to question the practice of averaging the mortality rate on the assumption that they are one disease. METHODS: A retrospective chart review of all patients diagnosed with SJS and TEN by a dermatologist between January 1, 2000, and January 1, 2020, at our institution was performed. Seventy-one patients were identified (21 pediatric and 50 adults). Pathology slides from 32 adult patients (64%) were evaluated by a blinded board-certified dermatopathologist. RESULTS: Of the adult patients, 31 had SJS, two had SJS-TEN overlap, and 17 had TEN. All 21 patients in the pediatric group were diagnosed with SJS mainly caused by Mycoplasma. Mortality rates were 6.5% for SJS among adults and 35.3% for TEN. Chemotherapy-induced TEN is a trigger with 50% mortality. CONCLUSIONS: SJS was more common in adults and pediatric cases than TEN (3:1) and had a much better prognosis and outcome. Combining and averaging the mortality rates of TEN and SJS are not advised as SJS is mainly a mucocutaneous disorder with good prognosis versus TEN, a systemic toxicity of multiple organs with deep skin detachment.

Disseminated intravascular coagulopathy: a complication of Stevens-Johnson syndrome/toxic epidermal necrolysis.

BACKGROUND: The purpose of this study was to retrospectively assess clinical characteristics and mortality rate of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients who developed disseminated intravascular coagulation (DIC). METHODS: A systematic retrospective chart review of all patients with concurrent clinical diagnosis of DIC and SJS/TEN between July 1, 2012, and January 1, 2020, at the Mayo Clinic was performed. RESULTS: The incidence of DIC in patients with SJS/TEN was 1.3% at our institution (5 of 396 DIC patients). Triggers of SJS/TEN included lamotrigine, clofarabine, antibiotics, and sepsis. Two patients diagnosed with SJS and two patients with TEN succumbed to the disease. CONCLUSION: DIC is a rare underlying risk in patients with SJS/TEN and is associated with increased mortality. Early clinician awareness and aggressive intervention is advised.