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Fulminant hemorrhagic ulcerative purpura as the first cutaneous manifestation of generalized granulomatosis with polyangiitis
5482
5613
Fulminant hemorrhagic ulcerative purpura as the first cutaneous manifestation of generalized granulomatosis with polyangiitis Margaret Wat, MD, University Hospitals Cleveland Medical Center, Case Western Reserve University; Kord Honda, MD, University Hospitals Cleveland Medical Center, Case Western Reserve University; Elma Baron, MD, University Hospitals Cleveland Medical Center, Case Western Reserve University
GallieGalli disease: A rare variant of DowlingeDegos disease Jack Cossman, MD, Roger Williams Medical Center; Laura Della Torre, MD, Roger Williams Medical Center; Rui Cheng, MD, Roger Williams Medical Center; Elizabeth Tocci, MD, Roger Williams Medical Center A 50-year-old woman presented with longstanding diffuse lentigines and pruritic erythematous papules on the trunk. Her father and sister had a similar skin condition, and her diagnosis for years was considered to be Grover’s disease. Treatment with topical steroids never provided complete relief. Skin biopsy demonstrated superficial acantholysis and lentiginous acanthosis, diagnostic features of GallieGalli disease. GallieGalli disease is a rare inherited variant of DowlingeDegos disease, but is histologically distinct and characterized clinically by 1-2 mm slightly keratotic red to dark brown papules that are focally confluent in a reticulate pattern. The disease is also characterized by slowly progressive and disfiguring reticulate hyperpigmentation of the flexures, clinically and histopathologically diagnostic for DowlingeDegos disease but also associated with suprabasal, nondyskeratotic acantholysis. The underlying genetic abnormality is a keratin 5 mutation. Treatment options are limited, but we report improvement in lentigines with IPL and improvement in acantholysis with highly potent topical steroid application. Combination treatment may be optimally beneficial.
A 52-year-old female former smoker presented with extensive ulcerative purpuric plaques which acutely enlarged over one week from small scattered purpuric macules around her ankles. She reported recurrent sinusitis, fatigue, worsening dyspnea, hemoptysis, peripheral neuropathy, and intermittent arthralgia. She had been recently hospitalized for Staphylococcus aureus pneumonia and newly identified extensive right lung consolidation and cavitation. Physical examination revealed multiple bullous and ulcerative purpuric plaques (largest diameter [15 cm) on distal legs, ankles, elbows, knees, and fingers, oral ulcers, and saddle-nose deformity. Pathology of two skin lesions showed a brisk neutrophilic infiltrate with eosinophils and fibrinoid degeneration suggestive of leukocytoclastic vasculitis. Lesional tissue culture grew no bacteria. Lung tissue biopsy revealed diffuse acute inflammation with histiocytes and giant cells without malignant cells, and multiple AFB sputum smears were negative. CT scan of paranasal sinuses demonstrated diffuse pan-sinus chronic inflammatory changes and nearly complete opacification of right mastoid and middle ear cavities. Urinalysis revealed hematuria and proteinuria. Positive cytoplasmic ANCA titer (1:320) with positive PR3 confirmed granulomatosis with polyangiitis (GPA). Cutaneous lesions, dyspnea, and sinusitis rapidly improved with intravenous methylprednisolone and rituximab. This case demonstrates that severe GPA can rarely present as fulminant ulcerative purpura as its first cutaneous manifestation.
Commercial support: None identified.
Commercial support: None identified.
5350 Function of family history in patchy alopecia patients: The Cleveland Clinic experience Sophie Wang, BS, Cleveland Clinic, Department of Dermatology; Rubina Ratnaparkhi, BS, Cleveland Clinic, Department of Dermatology; Melissa Piliang, MD, Cleveland Clinic, Department of Dermatology; Wilma Bergfeld, MD, Cleveland Clinic, Department of Dermatology Background: Positive family history of alopecia areata (AA) has been associated with universalis and totalis patterns, but its impact specifically in patchy alopecia (PA) patients remains unclear. The objective of this study was to evaluate the relationship of family history of AA with demographics, triggers, comorbidities, disease course, and response to treatment in the PA subtype. Methods: An IRB approved retrospective review of medical records was performed for 256 AA patients seen at the Cleveland Clinic from 2000-2016. Patients were classified as PA based on clinical assessment by hair specialist dermatologists based on the following criteria: 50% or less of initial scalp hair loss in a pattern of welldelineated patches. Data collected include demographics, comorbidities, disease severity, and response to treatment, and comparisons were drawn using Pearson chisquare tests, Fisher exact tests, Wilcoxon rank sum tests, and t tests as appropriate. Results: Stress and/or fatigue was the most common trigger among PA patients (35%). Other common triggers included illnesses (9.4%), thyroid abnormalities (3.9%), and seasonal changes (3.9%). Dermatologic comorbidities (dermatitis, acne) were the most common, followed by atopy (44.5%) and autoimmune disease (AI, 43.8%). Significantly fewer patients with family history of AA showed regrowth after relapse (89% vs 99%; P ¼.036). Patients with family history of AA were more likely to have abnormally high ferritin levels (P ¼.078) and positive microsomal antibodies (P ¼ .06) and less likely to have abnormally low zinc levels (P ¼ .052), though these comparisons did not reach statistical significance. Patients with family history of AA and family history of AI (lupus, vitiligo, Hashimoto’s thyroiditis, rheumatoid arthritis, diabetes) are more likely to have AI comorbidities (59% vs 7%; P ¼ .001), and have positive microsomal antibodies (50% vs 10%; P ¼ .030). Patients without family history of AA and positive family history of AI tended to be younger (28.0 6 19.1 vs 35.0 6 19.6; P ¼ .014) and more frequently had abnormally high ferritin levels (10.5% vs 1.9%; P ¼ .032).
5297 Gene expression analysis differentiates pediatric melanomas from Spitz nevi Burkhard Jansen, MD, DermTech; Doyle Hansen, MD, Pacific Pathology; Yao Zuxu, PhD, Dermtech Background: We recently validated a dermatology gene expression platform using adhesive patch biopsies to noninvasively collect skin samples. LINC (Long Intergeneic Non-Coding RNA 518) and/or PRAME (Preferentially Expressed Antigen in Melanoma) gene expression in adult patients differentiates primary melanomas from atypical nevi and other pigmented lesions with a NPV of over 99%, a sensitivity of 91% and a specificity of 69% to help clinicians with the management of difficult to assess pigmented lesions. Surgically obtained melanomas from adult patients show the same gene expression pattern. Approach: In this study we investigate gene expression patterns of pediatric pigmented lesions from FFPE tissue block samples with a focus on differentiating Spitz nevi from pediatric melanomas. Spitz nevi can pose significant diagnostic challenges to both clinicians and dermatopathologists when the current imagerecognition based gold standard is employed. Histopathologically confirmed samples of pediatric melanomas, pediatric nevi and pediatric Spitz nevi (n ¼ 8-9 per group) were assessed by qRT-PCR for LINC, PRAME and 4 control genes.
Conclusion: Family history of AA is associated with reduced regrowth after relapse in patchy AA. AI disease is associated with an earlier age of onset independent of family history. This study also elucidated common triggers (stress, illnesses, thyroid abnormalities, seasonal changes) and comorbidities (dermatologic comorbidities, atopy, AI) in PA patients.
Results: Consistent with findings in adults, PRAME levels were significantly (P \ .001) increased based on normalized Ct cycle counts (lower cycle counts indicate higher expression levels) in pediatric melanomas (mean Ct 33.45 + 0.61, 95% CI 32.35-34.56) when compared to Spitz (37.14 + 0.99, 95% CI, 35.81-38.47) or common nevi (37.21 + 0.80, 95% CI, 35.73-38.69), respectively. LINC levels were, again consistent with findings in adults, also increased in pediatric melanomas whereas 4 control genes (ACTB, B2M, CMIP and PPIA) showed similar expression levels in all 3 pigmented lesion groups investigated. Clinically and histopathologically complex pediatric Spitz nevi demonstrated gene expression signatures almost identical to gene expression signatures of common pediatric nevi but different from pediatric melanomas. Conclusion: PRAME and LINC gene expression can be valuable objective aids to differentiate pediatric melanomas from Spitz nevi, groups of pigmented lesions that can be particularly difficult to assess in children.
Commercial support: None identified.
Commercial support: Supported by DermTech, Inc.
JUNE 2017
J AM ACAD DERMATOL
AB143
5613
Fulminant hemorrhagic ulcerative purpura as the first cutaneous manifestation of generalized granulomatosis with polyangiitis Margaret Wat, MD, University Hospitals Cleveland Medical Center, Case Western Reserve University; Kord Honda, MD, University Hospitals Cleveland Medical Center, Case Western Reserve University; Elma Baron, MD, University Hospitals Cleveland Medical Center, Case Western Reserve University
GallieGalli disease: A rare variant of DowlingeDegos disease Jack Cossman, MD, Roger Williams Medical Center; Laura Della Torre, MD, Roger Williams Medical Center; Rui Cheng, MD, Roger Williams Medical Center; Elizabeth Tocci, MD, Roger Williams Medical Center A 50-year-old woman presented with longstanding diffuse lentigines and pruritic erythematous papules on the trunk. Her father and sister had a similar skin condition, and her diagnosis for years was considered to be Grover’s disease. Treatment with topical steroids never provided complete relief. Skin biopsy demonstrated superficial acantholysis and lentiginous acanthosis, diagnostic features of GallieGalli disease. GallieGalli disease is a rare inherited variant of DowlingeDegos disease, but is histologically distinct and characterized clinically by 1-2 mm slightly keratotic red to dark brown papules that are focally confluent in a reticulate pattern. The disease is also characterized by slowly progressive and disfiguring reticulate hyperpigmentation of the flexures, clinically and histopathologically diagnostic for DowlingeDegos disease but also associated with suprabasal, nondyskeratotic acantholysis. The underlying genetic abnormality is a keratin 5 mutation. Treatment options are limited, but we report improvement in lentigines with IPL and improvement in acantholysis with highly potent topical steroid application. Combination treatment may be optimally beneficial.
A 52-year-old female former smoker presented with extensive ulcerative purpuric plaques which acutely enlarged over one week from small scattered purpuric macules around her ankles. She reported recurrent sinusitis, fatigue, worsening dyspnea, hemoptysis, peripheral neuropathy, and intermittent arthralgia. She had been recently hospitalized for Staphylococcus aureus pneumonia and newly identified extensive right lung consolidation and cavitation. Physical examination revealed multiple bullous and ulcerative purpuric plaques (largest diameter [15 cm) on distal legs, ankles, elbows, knees, and fingers, oral ulcers, and saddle-nose deformity. Pathology of two skin lesions showed a brisk neutrophilic infiltrate with eosinophils and fibrinoid degeneration suggestive of leukocytoclastic vasculitis. Lesional tissue culture grew no bacteria. Lung tissue biopsy revealed diffuse acute inflammation with histiocytes and giant cells without malignant cells, and multiple AFB sputum smears were negative. CT scan of paranasal sinuses demonstrated diffuse pan-sinus chronic inflammatory changes and nearly complete opacification of right mastoid and middle ear cavities. Urinalysis revealed hematuria and proteinuria. Positive cytoplasmic ANCA titer (1:320) with positive PR3 confirmed granulomatosis with polyangiitis (GPA). Cutaneous lesions, dyspnea, and sinusitis rapidly improved with intravenous methylprednisolone and rituximab. This case demonstrates that severe GPA can rarely present as fulminant ulcerative purpura as its first cutaneous manifestation.
Commercial support: None identified.
Commercial support: None identified.
5350 Function of family history in patchy alopecia patients: The Cleveland Clinic experience Sophie Wang, BS, Cleveland Clinic, Department of Dermatology; Rubina Ratnaparkhi, BS, Cleveland Clinic, Department of Dermatology; Melissa Piliang, MD, Cleveland Clinic, Department of Dermatology; Wilma Bergfeld, MD, Cleveland Clinic, Department of Dermatology Background: Positive family history of alopecia areata (AA) has been associated with universalis and totalis patterns, but its impact specifically in patchy alopecia (PA) patients remains unclear. The objective of this study was to evaluate the relationship of family history of AA with demographics, triggers, comorbidities, disease course, and response to treatment in the PA subtype. Methods: An IRB approved retrospective review of medical records was performed for 256 AA patients seen at the Cleveland Clinic from 2000-2016. Patients were classified as PA based on clinical assessment by hair specialist dermatologists based on the following criteria: 50% or less of initial scalp hair loss in a pattern of welldelineated patches. Data collected include demographics, comorbidities, disease severity, and response to treatment, and comparisons were drawn using Pearson chisquare tests, Fisher exact tests, Wilcoxon rank sum tests, and t tests as appropriate. Results: Stress and/or fatigue was the most common trigger among PA patients (35%). Other common triggers included illnesses (9.4%), thyroid abnormalities (3.9%), and seasonal changes (3.9%). Dermatologic comorbidities (dermatitis, acne) were the most common, followed by atopy (44.5%) and autoimmune disease (AI, 43.8%). Significantly fewer patients with family history of AA showed regrowth after relapse (89% vs 99%; P ¼.036). Patients with family history of AA were more likely to have abnormally high ferritin levels (P ¼.078) and positive microsomal antibodies (P ¼ .06) and less likely to have abnormally low zinc levels (P ¼ .052), though these comparisons did not reach statistical significance. Patients with family history of AA and family history of AI (lupus, vitiligo, Hashimoto’s thyroiditis, rheumatoid arthritis, diabetes) are more likely to have AI comorbidities (59% vs 7%; P ¼ .001), and have positive microsomal antibodies (50% vs 10%; P ¼ .030). Patients without family history of AA and positive family history of AI tended to be younger (28.0 6 19.1 vs 35.0 6 19.6; P ¼ .014) and more frequently had abnormally high ferritin levels (10.5% vs 1.9%; P ¼ .032).
5297 Gene expression analysis differentiates pediatric melanomas from Spitz nevi Burkhard Jansen, MD, DermTech; Doyle Hansen, MD, Pacific Pathology; Yao Zuxu, PhD, Dermtech Background: We recently validated a dermatology gene expression platform using adhesive patch biopsies to noninvasively collect skin samples. LINC (Long Intergeneic Non-Coding RNA 518) and/or PRAME (Preferentially Expressed Antigen in Melanoma) gene expression in adult patients differentiates primary melanomas from atypical nevi and other pigmented lesions with a NPV of over 99%, a sensitivity of 91% and a specificity of 69% to help clinicians with the management of difficult to assess pigmented lesions. Surgically obtained melanomas from adult patients show the same gene expression pattern. Approach: In this study we investigate gene expression patterns of pediatric pigmented lesions from FFPE tissue block samples with a focus on differentiating Spitz nevi from pediatric melanomas. Spitz nevi can pose significant diagnostic challenges to both clinicians and dermatopathologists when the current imagerecognition based gold standard is employed. Histopathologically confirmed samples of pediatric melanomas, pediatric nevi and pediatric Spitz nevi (n ¼ 8-9 per group) were assessed by qRT-PCR for LINC, PRAME and 4 control genes.
Conclusion: Family history of AA is associated with reduced regrowth after relapse in patchy AA. AI disease is associated with an earlier age of onset independent of family history. This study also elucidated common triggers (stress, illnesses, thyroid abnormalities, seasonal changes) and comorbidities (dermatologic comorbidities, atopy, AI) in PA patients.
Results: Consistent with findings in adults, PRAME levels were significantly (P \ .001) increased based on normalized Ct cycle counts (lower cycle counts indicate higher expression levels) in pediatric melanomas (mean Ct 33.45 + 0.61, 95% CI 32.35-34.56) when compared to Spitz (37.14 + 0.99, 95% CI, 35.81-38.47) or common nevi (37.21 + 0.80, 95% CI, 35.73-38.69), respectively. LINC levels were, again consistent with findings in adults, also increased in pediatric melanomas whereas 4 control genes (ACTB, B2M, CMIP and PPIA) showed similar expression levels in all 3 pigmented lesion groups investigated. Clinically and histopathologically complex pediatric Spitz nevi demonstrated gene expression signatures almost identical to gene expression signatures of common pediatric nevi but different from pediatric melanomas. Conclusion: PRAME and LINC gene expression can be valuable objective aids to differentiate pediatric melanomas from Spitz nevi, groups of pigmented lesions that can be particularly difficult to assess in children.
Commercial support: None identified.
Commercial support: Supported by DermTech, Inc.
JUNE 2017
J AM ACAD DERMATOL
AB143