Clinical Characteristics and Inciting Agents for Pseudoporphyria: The Mayo Clinic Experience, 1996-2020.

GENERAL PURPOSE: To raise awareness regarding the clinical presentations of patients with pseudoporphyria. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will:1. Describe the clinical presentation of pseudoporphyria.2. Identify the differential diagnoses of blistering lesions on hands and feet.3. Outline the management options for patients with porphyria.

Pseudoporphyria is an uncommon immunobullous disease that is clinically and histopathologically similar to porphyria cutanea tarda but without abnormal porphyrin levels. Limited case reports and case series of pseudoporphyria have been published. To describe the clinical characteristics and inciting agents for patients with pseudoporphyria. Health records were retrospectively reviewed for patients treated at an integrated multiregional health system from 1996 through 2020. To report results, the authors used descriptive statistics, median (range) for continuous variables, and number (percentage) for categorical data. In total, 23 patients met the inclusion criteria: 13 men and 10 women. The most common medications causing pseudoporphyria were nonsteroidal anti-inflammatory drugs, the antihypertensive agent hydrochlorothiazide, and retinoids. All patients had blisters and reported photosensitivity. Seven patients (30.4%) also had scarring, and one (4.3%) had milia. All patients had normal porphyrin levels in their serum, urine, and stool. Among patients with remission, symptoms resolved at a median of 2.5 months (range, 1 week to 24 months) after discontinuation of the suspected inciting medication. Four patients, however, had persistent symptoms at a median of 6 months (range, 2­9 months). Because pseudoporphyria is a diagnosis of exclusion, clinicians should familiarize themselves with the presentation and management of this uncommon condition.

Histopathologic features predictive of perivascular deposition of IgA on direct immunofluorescence in cases of leukocytoclastic vasculitis: A retrospective study of 112 specimens.

IgA vasculitis is a small-vessel vasculitis subtype with increased risk of systemic involvement. We aimed to investigate if any light-microscopic features can predict the presence of perivascular granular IgA deposits on direct immunofluorescence (DIF) microscopy. We performed a retrospective search of cutaneous pathology reports from our internal and consultation practice (January 1, 2010-October 5, 2021) with a diagnosis of leukocytoclastic vasculitis and accompanying DIF. A blinded dermatopathologist reviewed standard microscopy slides for predetermined histopathological features. Fifty-six biopsies (48 patients) and 56 biopsies (42 patients) met inclusion criteria for IgA+ and IgA-, respectively. The presence of eosinophils and mid and deep dermal inflammation were statistically more associated with IgA- (41/56 [73.2%] and 31/56 [55.4%], respectively) than IgA+ cases (28/56 [50.0%] and 14/56 [25.0%]; p = 0.049 and 0.006, respectively, chi-squared test). Other microscopic criteria recorded were not significantly different between the two groups (p > 0.05, chi-squared and Fisher's exact tests). In this retrospective study of 112 cases, we found that while the absence of eosinophils and absence of mid- and deep inflammation were correlated with increased likelihood of IgA perivascular deposition on DIF, no other histopathological features on light microscopy tested could reliably predict the presence of IgA perivascular deposition on DIF. Therefore, DIF remains a necessary component for the accurate diagnosis of cutaneous IgA vasculitis.

Do histopathological features correlate with systemic manifestations in dermatomyositis? Analysis of 42 skin biopsy specimens from 22 patients.

BACKGROUND: Understanding whether specific histopathologic features on skin biopsy are predictive of systemic associations in dermatomyositis (DM) would be useful to guide clinical screening. METHODS: Through retrospective medical record search, clinical and laboratory findings of patients with DM were documented. Existing skin biopsy slides were re-reviewed blindly. RESULTS: Of all biopsy specimens (n = 42), the most frequent histopathological finding was vacuolar interface dermatitis (95%). Other features included perivascular lymphocytic infiltrate (71%), increased dermal mucin (40%), vessel wall thickening (12%), follicular plugging (9.5%), and dermal sclerosis (7%). Neutrophilic infiltrate was observed in three biopsies from a patient with adalimumab-associated DM. Vasculitis was not observed. There was no statistically significant difference in the presence of any histopathological feature and that of various systemic manifestations (i.e., myopathy, interstitial lung disease [ILD] and malignancy). However, we observed that dense lichenoid infiltrate rather than pauci-inflammatory changes correlated with severe itching (p < 0.001). Patients with MDA-5 antibodies were significantly more likely to have vasculopathy than those without (p = 0.029*). CONCLUSIONS: No dermatopathologic feature was reliably predictive of myopathy, ILD, or malignancy. This finding implies that, regardless of histopathologic findings, patients should be screened for associated conditions as clinically indicated.

A detailed analysis of the distribution, morphology, and histopathology of complex purpura in hospitalized patients: A case series of 68 patients.

BACKGROUND: Purpura in inpatients commonly leads to dermatologic consultation. The differential diagnosis is broad and algorithms are intricate. OBJECTIVE: We evaluated inpatient consultations for complex purpura to document the most common diagnoses and to validate the true diagnostic utility of histopathology, clinical morphology, and distribution. METHODS: We reviewed a case series of 68 inpatients during a 4-year period with a dermatologic consultation for purpura and biopsy findings of vasculitis or microvascular occlusion. RESULTS: Key features of complex purpura are nonbranching (round) versus branching (retiform) morphology, dependent versus acral or generalized distribution, and leukocytoclastic vasculitis versus microvascular occlusion (with emphasis on depth of involvement). Dependent nonbranching purpura with only superficial vessels involved by leukocytoclastic vasculitis was most often due to IgA vasculitis or cutaneous single-organ small-vessel vasculitis. In contrast, deeper involvement by leukocytoclastic vasculitis was suggestive of systemic disease (eg, antineutrophil cytoplasmic antibody-associated vasculitis). Branching purpura was concerning, with greater than 90% sensitivity and specificity for microvascular occlusion and associated high mortality (≈50%). The majority of patients who died had acral branching lesions. LIMITATIONS: Small sample size, inpatients at a tertiary care center, and retrospective nature are some limitations. CONCLUSION: Nonbranching dependent purpura corresponded to leukocytoclastic vasculitis, with the most common diagnoses being IgA vasculitis or skin-limited small-vessel vasculitis; patients with deep involvement often had systemic diseases. In this series, branching purpura was due to microvascular occlusion rather than medium-vessel vasculitis, and had associated high mortality.

Use of teledermatology by dermatology hospitalists is effective in the diagnosis and management of inpatient disease.

BACKGROUND: Patient outcomes are improved when dermatologists provide inpatient consultations. Inpatient access to dermatologists is limited, illustrating an opportunity to use teledermatology. Little is known about the ability of dermatologists to accurately diagnose disease and manage inpatients with teledermatology, particularly when using nondermatologist-generated clinical data. METHODS: This prospective study assessed the ability of teledermatology to diagnose disease and manage 41 dermatology consultations from a large urban tertiary care center, using internal medicine referral documentation and photographs. Twenty-seven dermatology hospitalists were surveyed. Interrater agreement was assessed by the κ statistic. RESULTS: There was substantial agreement between in-person and teledermatology assessment of the diagnosis with differential diagnosis (median κ = 0.83), substantial agreement in laboratory evaluation decisions (median κ = 0.67), almost perfect agreement in imaging decisions (median κ = 1.0), and moderate agreement in biopsy decisions (median κ = 0.43). There was almost perfect agreement in treatment (median κ = 1.0), but no agreement in follow-up planning (median κ = 0.0). There was no association between raw photograph quality and the primary plus differential diagnosis or primary diagnosis alone. LIMITATIONS: Selection bias and single-center nature. CONCLUSIONS: Teledermatology may be effective in the inpatient setting, with concordant diagnosis, evaluation, and management decisions.

Evolution of Dupilumab-Associated Cutaneous Atypical Lymphoid Infiltrates.

BACKGROUND: Observations highlighting the "unmasking" of cutaneous T-cell lymphoma after treatment with dupilumab for atopic dermatitis (AD) have been recently reported. However, there remains a paucity of literature describing the evolution of clinical and histopathological features that characterizes this phenomenon. OBJECTIVE: To define the clinical and histopathologic evolution of atypical lymphoid infiltrates after the administration of dupilumab for AD. METHODS: A cross-sectional study of clinical and histopathologic features in 7 consecutive patients with a diagnosis of "atypical lymphoid infiltrate" or mycosis fungoides (MF) on dupilumab for AD was performed. RESULTS: Seven patients with atypical lymphoid infiltrates or MF in evolution after dupilumab therapy (age range 27-74 years) were reviewed. Average duration of AD before MF diagnosis was 5.7 years, and the average duration on dupilumab treatment was 9.8 months. Notable histopathologic features across predupilumab and postdupilumab biopsies included progressive increase in the densities of the atypical lymphoid infiltrates (7/7), presence of atypical epidermotropic lymphocytes (6/7), and papillary dermal fibrosis (6/7). LIMITATIONS: Small retrospective cohort study. CONCLUSION: These cases highlight the transformation of lymphoid infiltrates after dupilumab treatment for AD and emphasize the importance of clinical and histopathologic evaluation before and during treatment with dupilumab for treatment-refractory presumed AD.

Use of spironolactone to treat acne in adolescent females.

BACKGROUND/OBJECTIVES: Studies assessing the utility of spironolactone for treating acne in adolescent females are lacking. Thus, we sought to examine spironolactone's role in treating this patient population. METHODS: A retrospective review was performed to determine the efficacy of spironolactone treatment in adolescent females seen at Mayo Clinic in Rochester, Minnesota, from 2007 to 2017. RESULTS: In a cohort of 80 pediatric patients with a median age of 19 years (range, 14-20 years), 64 patients (80%) experienced improvement of acne on treatment with spironolactone (median dose, 100 mg daily) with a favorable side effect profile. Approximately a quarter of patients (22.5%) had a complete response; more than half (58.8%) had a complete response or a partial response greater than 50%. Initial and maximal responses were observed at a median of 3 months and 5 months, respectively. Patients received treatment with spironolactone for a median duration of 7 months (range, 3-45 months) with limited side effects. CONCLUSIONS: Spironolactone demonstrated efficacy in treating acne in adolescent females and is a safe long-term alternative to systemic antibiotics in these patients.

Multicentric reticulohistiocytosis: the Mayo Clinic experience (1980-2017).

OBJECTIVES: Multicentric reticulohistiocytosis (MRH), a rare histiocytic disease that can mimic other rheumatic conditions, may be associated with cancer and other autoimmune disorders. To better understand the disorder and its other associations, we aimed to evaluate clinical correlates and outcomes of all patients with MRH seen at Mayo Clinic, Rochester between 1980 and 2017. METHODS: A retrospective medical record review was conducted to identify all patients with MRH between 1 January 1980 and 30 April 2017. RESULTS: We identified 24 patients with biopsy-proven MRH (58% female, 75% Caucasian, median age at diagnosis 52 years, median follow-up of 2.3 years). All patients had cutaneous and articular involvement; 23 (96%) patients had papulonodular skin lesions (87% periungual and dorsal hand) and seven (30%) mucosal nodules; and 22 (92%) patients had arthralgias, 21 (88%) joint effusions and 13 (54%) synovitis. Most frequently used therapies included corticosteroids, cyclophosphamide, methotrexate and bisphosphonates. Biologics were used in four patients. Nine patients had symptomatic resolution at 1 year and 12 partial improvement. Radiological findings included erosive changes in three (60%) patients and arthritis mutilans in two patients (40%). Twenty-nine per cent of patients had a concomitant autoimmune disease and 25% malignancy including melanoma, endometrial, peritoneal and lung carcinoma. The 5-year survival rate was 85% (95% CI: 74, 100%). CONCLUSION: To our knowledge, this is the largest single-centre series of patients with MRH highlighting the rarity of the condition and an unmet need for treatment options that can allow sustained disease remission. It also highlights the need for a high vigilance for malignancy and autoimmune diseases.

Pyoderma gangrenosum in hematologic malignancies: A systematic review.

BACKGROUND: Pyoderma gangrenosum (PG) is a devastating neutrophilic dermatosis that may be associated with trauma or systemic diseases. The associations, characteristics, and temporal relationship of PG with hematologic malignancies are not well understood. OBJECTIVE: We performed a systematic review of PG associated with hematologic malignancies using data from case reports, case series, and retrospective studies. METHODS: We searched MEDLINE, EMBASE, Scopus, and Web of Science from each database's inception to December 12, 2018. Two reviewers independently selected studies and extracted data. RESULTS: Two hundred seventy-nine publications met the inclusion criteria (340 cases). Myelodysplastic syndrome (MDS) was the most commonly reported hematologic malignancy associated with PG, followed by monoclonal gammopathy of undetermined significance and acute myeloid leukemia. The mean age of patients was 56.5 years, with males being more common. There was a predominance of the ulcerative PG subtype and multifocal distributions across all hematologic malignancies. The majority of MDS cases preceded PG, which was reversed for MGUS. LIMITATIONS: The data were limited by reporting bias because PG subtypes rely on the rendered diagnosis reported. In addition, the classification for hematologic malignancies has evolved since 1978. CONCLUSION: Patients with PG should be evaluated for hematologic malignancies, with MDS being the most common.

Society of Dermatology Hospitalists supportive care guidelines for the management of Stevens-Johnson syndrome/toxic epidermal necrolysis in adults.

Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are life-threatening conditions with high morbidity and mortality. Supportive care management of SJS/TEN is highly variable. A systematic review of the literature was performed by dermatologists, ophthalmologists, intensivists, and gynecologists with expertise in SJS/TEN to generate statements for supportive care guideline development. Members of the Society of Dermatology Hospitalists with expertise in SJS/TEN were invited to participate in a modified, online Delphi-consensus. Participants were administered 9-point Likert scale questionnaires regarding 135 statements. The RAND/UCLA Appropriateness Method was used to evaluate and select proposed statements for guideline inclusion; statements with median ratings of 6.5 to 9 and a disagreement index of ≤1 were included in the guideline. For the final round, the guidelines were appraised by all of the participants. Included are an evidence-based discussion and recommendations for hospital setting and care team, wound care, ocular care, oral care, urogenital care, pain management, infection surveillance, fluid and electrolyte management, nutrition and stress ulcer prophylaxis, airway management, and anticoagulation in adult patients with SJS/TEN.

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.

Schnitzler Syndrome With Delirium and Vertigo: The Utility of Neurologic Manifestations in Diagnosis.

Schnitzler syndrome (SS) is an autoinflammatory dermatosis that often goes undiagnosed for 5-6 years. Patients typically carry a diagnosis of urticaria; however, their cutaneous symptoms fail to respond to typical urticaria therapies and lack symptoms such as pruritus. Additionally, patients with SS may see multiple providers for nonspecific complaints of fever, lymphadenopathy, arthralgias, and bone pain. A correct diagnosis is paramount, as close to 20% of patients may develop a lymphoproliferative disorder and appropriate treatment may ameliorate all symptoms.1 We report 2 cases of SS misdiagnosed as urticaria for years in order to illuminate diagnostic pearls, histopathological findings, and treatment modalities. Additionally, we highlight the importance of neurologic disturbances in this rare but important differential diagnosis of urticaria.

J Drugs Dermatol. 2017;16(6):625-627.

Generalized Discoid Lupus Erythematosus as the Presenting Sign of Small Cell Lung Carcinoma.

A 46-year-old woman with a 30 pack-year smoking history presented with a worsening eruption on the left cheek that failed to improve with metronidazole gel. The cutaneous eruption spread to most of her face and did not respond to a brief tapering course of prednisone. During the initial evaluation at our institution, approximately 6 weeks after the onset of the cutaneous eruption, the patient had erythematous, crusted plaques on her face and scalp (Figure 1A); they were also present on the V-area of the anterior aspect of the neck and upper region of the chest, the shoulders, and the arms, with isolated lesions on the trunk and legs. Her oral mucosa had erythematous erosions on the hard palate and gingivae. A review of systems revealed pain and burning of her skin lesions, but no muscle weakness or other systemic clinical manifestations. The differential diagnosis included autoimmune connective tissue disease, pemphigus foliaceous, sarcoidosis, lichen planus, phototoxic drug eruption, and eczema herpeticum.

Hidradenitis Suppurativa in Patients With Inflammatory Bowel Disease: A Population-Based Cohort Study in Olmsted County, Minnesota.

BACKGROUND & AIMS: Patients with inflammatory bowel disease (IBD) may be at higher risk for hidradenitis suppurativa (HS). We studied the risk and clinical characteristics of HS in a population-based cohort of patients with IBD. METHODS: We identified all cases of HS (confirmed by biopsy and/or dermatologic evaluation) in a population-based inception cohort of Olmsted County, Minnesota, residents diagnosed with IBD between 1970 and 2004 and followed up through August 2013. We estimated the incidence rate ratio of HS in patients with IBD compared with the general population, and described the clinical characteristics, risk factors, and management of HS. RESULTS: In 679 IBD patients followed up over a median of 19.8 years, we identified 8 patients with HS (mean age, 44.4 ± 8.3 y; 7 women; 6 obese). Compared with the general population, the incidence rate ratio of HS in IBD was 8.9 (95% confidence interval, 3.6-17.5). The 10- and 30-year cumulative incidence of HS was 0.85% and 1.55%, respectively. Five patients had Crohn's disease, 4 of whom had perianal disease; of 3 patients with ulcerative colitis, 2 had undergone ileal pouch-anal anastomosis. Axillae, groin, and thighs were the most common sites of involvement. Six patients had Hurley stage 2 disease (recurrent abscesses with sinus tracts and scarring, involving widely separated areas), and required a combination of antibiotics and surgery; none of the patients were treated with anti-tumor necrosis factor-α agents. CONCLUSIONS: In this population-based study, patients with IBD were approximately 9 times more likely to develop HS than the general population, with a female predisposition.

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.

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.

Frozen section diagnosis for non-melanoma skin cancers: correlation with permanent section diagnosis.

Frozen section pathology is routinely used for margin assessment of non-melanoma skin cancer (NMSC). Frozen section can also be used for the primary diagnosis of several skin lesions. Limited data exist on the accuracy of frozen section in the diagnosis of NMSC. We performed a retrospective chart review of 300 cases in which frozen section diagnoses were compared with permanent section diagnoses of NMSC. Frozen section and permanent section pathology were concordant 83.3% of the time, with the highest concordance rates noted for basal cell carcinoma (145/153, 95%). Our results show a high level of concordance between frozen section and corresponding permanent section pathology diagnosis for NMSC. The rapidity of frozen section tissue processing and pathology reporting makes this technique useful in dermatologic practice for immediate diagnosis and management of NMSC. Further studies should explore strategies to decrease or eliminate discrepancies between frozen and permanent section diagnosis.

Vasospasm Is a Consistent Finding in Pernio (Chilblains) and a Possible Clue to Pathogenesis.

BACKGROUND/AIMS: Pernio (chilblains) is an inflammatory condition classically characterized by localized erythema and swelling of acral sites upon exposure to cool and damp conditions. We sought to determine whether cold-induced vasospasm has a role in the development of pernio. METHODS: We retrospectively reviewed 5 patients with pernio who were seen at our institution between January 1, 2000 and December 31, 2011, and had undergone a noninvasive arterial vascular study of the upper extremities that corresponded to a site of clinical involvement of pernio and who had also undergone vasospastic testing and ice water immersion as part of the noninvasive arterial vascular study protocol. RESULTS: Vascular testing in all patients (mean age 37.8 years; 4 women) demonstrated vasospasm with ice water immersion. CONCLUSION: Our findings suggest that vasospasm likely has a role in the pathophysiology of pernio and may also provide a rationale for the pharmacological treatment of vasospasm in patients with pernio.