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Eczematous skin reaction after intravenous immunoglobulin (IVIG) therapy
804
715
Differentiating confluent and reticulated papillomatosis from acanthosis nigricans Young Joon Park, MD, Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea; Sang Jin Kim, MD, Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea; Hee Young Kang, MD, PhD, Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea; Eun-So Lee, MD, PhD, Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea; You Chan Kim, MD, PhD, Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea
Eczematous skin reaction after intravenous immunoglobulin (IVIG) therapy Jing Zhang, MD, Drexel Dermatology, Philadelphia, PA, United States; Carrie Ann Cusack, MD, Drexel Dermatology, Philadelphia, PA, United States
Background: Confluent and reticulated papillomatosis (CRP) is an uncommon dermatosis manifesting as papules that coalesce to form a reticular pattern. Because its histopathologic features are similar to those of benign acanthosis nigricans (bAN), differentiation between CRP and bAN can be challenging. Thus, we compared the clinicopathologic characteristics of CRP and bAN. Methods: We retrospectively reviewed 60 CRP and 30 AN patients. Clinical characteristics included age, sex, morphology, location, symptoms, associated conditions, duration, treatment, treatment response, and weight. Histologic examinations were conducted on 33 CRP and 30 AN lesions. Brown-Brenn Gram staining, periodic acid-Schiff (PAS) staining, and immunohistochemistry were used to identify relevant microorganisms or differential markers. Results: While CRP lesions were concentrated on the trunk, AN lesions also appeared in flexure areas, such as the axilla. The high prevalence of AN in obese subjects was consistent with previous studies. Increases in Ki-67 and keratin 16 expression did not differ significantly between CRP and AN lesions. CRP lesions did not show significant positivity compared to AN lesions with the PAS stain. Bacteria were detected at a higher rate in CRP lesions than in normal skin, with no difference between CRP and AN lesions. On Fontana-Masson and gp100 staining, pigmentation was significantly greater in AN lesions than in CRP lesions, showing more melanocytes. Conclusion: The location of skin lesions and BMI are the main clinical differentiating factors between CRP and AN. The epidermal histologic changes of CRP are milder than those of AN. AN also showed a greater degree of pigmentation and melanocytic proliferation. High detection rates of bacteria in the lesion-affected skin of CRP support the speculation that bacteria may play a role in the pathogenesis of CRP.
A 74-year-old Caucasian male with a medical history of stage 0 chronic lymphocytic leukemia (diagnosed 10/2010), stage T1c prostate cancer and chronic inflammatory demyelinating polyneuropathy undergoing IVIG therapy presented with a diffuse itchy rash that developed 3 hours after his sixth IVIG infusion. The eruption started on the upper chest and spread peripherally over several days. Two days after the eruption started, the patient went to the ED where he was prescribed prednisone along with clotrimazole cream topically without benefit. The patient otherwise reported his usual state of health. His other medications include aspirin, finasteride, losartan, omeprazole, simvastatin and tamsulosin. The patient’s physical examination revealed diffuse, confluent, scaling pink papules on the face, trunk, upper extremities and hands bilaterally. A biopsy from the right upper extremity was consistent with spongiotic dermatitis. The patient was diagnosed with an eczematous drug eruption secondary to IVIG and is being treated with topical steroids and oral antihistamines. He is now much improved. Intravenous immunoglobulin is increasingly utilized both on- and off-label for a host of conditions including dermatologic, neurologic, hematologic and immunologic disorders. This case highlights a potential adverse side effects from IVIG. Most side effects tend to be minor with about 30-40% of patients experiencing headaches, chills, fatigue, nausea, arthralgias, myalgias and back pain. In rare instances, serious reactions do occur, which include aseptic meningitis, renal failure, anaphylactic shock, hemolytic anemia and thrombosis. Cutaneous side effects from IVIG occur in only an estimated 0.4 - 6% of patients and range from localized to generalized eruptions. The reported reactions include vasculitis, urticaria, erythema multiforme, alopecia, lichenoid dermatitis, purpuric erythema and morbilliform eruptions. A newer and possibly underreported side effect is an eczematous eruption seen in our patient. It is important to be cognizant of this side effect in the practice of dermatology as it may be encountered with increasing frequency due to the expanding use of IVIG. Commercial support: None identified.
Commercial support: None identified.
631
1990 Diffuse dermal angiomatosis Aleta Simmons, MD, MS, University Hospitals/Case Western Reserve University, Cleveland, OH, United States; Pezhman Shoureshi, DO, University Hospitals/Case Western Reserve University, Cleveland, OH, United States; Kord Honda, MD, University Hospitals/Case Western Reserve University, Cleveland, OH, United States A 46-year-old woman with a history of recurrent bilateral anterior granulomatous uveitis treated with mycophenolate presented two weeks after a biopsy of the right breast for a suspicious growth. The surgical scar was intact but she noticed a gradual development of an enlarging, painful, nonhealing lesion surrounding the surgical scar. Examination revealed a linear surgical scar with an overlying ulcerated plaque with a hyperpigmented border on the right breast inferior to the nipple. An ANA panel was positive for La/SSB antibody. Histology revealed vascular proliferation composed of spindle-shaped endothelial cells with focal small blood vessel formation involving the superficial dermis and extending into deeper portions of the dermis focally, around adnexal structures, and dermal collagen bundles. Based on histology she was diagnosed with diffuse dermal angiomatosis (DDA). The patient improved with intralesional steroids and topical clobetasol. Prednisone was deferred due to her history of glaucoma. She has been taking pentoxifylline 400 mg orally three times a day without evidence of new lesions. DDA is a rare, benign, acquired condition characterized by diffuse proliferation of CD31 and CD34 positive endothelial cells within the dermis causing tender or painful plaques with central ulceration. Based on its histologic hallmark, it is classified as a cutaneous reactive angiomatosis. Clinically, the condition may resemble pyoderma gangrenosum when located near a surgical scar. Histologically, DDA may resemble Kaposi sarcoma, angiosarcoma, and acroangiodermatitis. DDA is associated with comorbidities that predispose patients to hypercoagulable states, such as hypertension, diabetes mellitus, peripheral artery disease, or cardiovascular disease. Smoking also contributes to development of the condition in these patients. The specific pathogenesis of DDA is unknown. DDA affects middle-aged female smokers with a history of vascular disease. Although, there was a case involving one male patient and two cases of patients without vascular disease. This patient is the first reported case involving a history of granulomatous uveitis and positive La/SSB antibodies. Treatment options include reversal of contributing factors including smoking cessation, weight loss, arterial stenting or bypass, reduction mammoplasty, initiation of antithrombotic medications such as aspirin and pentoxifylline, or starting isotretinoin which has a fibrinolytic effect. Commercial support: None identified.
MAY 2015
Efficacy and safety of adalimumab in patients with moderate to severe hidradenitis suppurativa: Results from PIONEER II, a phase 3, randomized, placebo-controlled trial Gregor Jemec, University of Copenhagen, Roskilde, Denmark; Alice Gottlieb, Tufts Medical Center, Boston, MA, United States; Seth Forman, Forward Clinical Trials, Tampa, FL, United States; Evangelos Giamarellos-Bourboulis, 4th Department of Internal Medicine, Athens, Greece; Ziad Reguiai, CHU de Reims, H^ opital Robert Debre, Service de Dermatologie, Reims Cedex, France; Yihua Gu, AbbVie Inc, North Chicago, IL, United States; Martin Okun, AbbVie Inc, North Chicago, IL, United States Introduction: PIONEER II evaluated the safety and efficacy of adalimumab (ADA) vs placebo (PBO) in patients (pts) with moderate to severe hidradenitis suppurativa (HS). Data from the first 12 weeks (wks) are reported. Methods: This multicenter study included a 12-wk double-blind PBO-controlled period (PerA). Pts were randomized 1:1 to blinded ADA 40mg weekly starting at Wk4 (following 160 mg at Wk0; 80 mg at Wk2) or matching PBO. At baseline (BL), pts had a diagnosis of HS for $1 year, a total abscess and inflammatory nodule (AN) count of $3, HS lesions in $2 body areas (1 at Hurley Stage II or III) and had no prior TNF-a inhibitor treatment. PerA efficacy was analyzed for all randomized pts (intentto-treat [ITT_A Population]); safety was analyzed for the ITT_A Population who received $1 dose of study drug. The primary endpoint was HiSCR (HS Clinical Response; $50% reduction from BL in AN count and no increase in abscess or in draining fistula counts) at Wk12. Results: Of the 326 in the ITT_A Population, 67.8% were women; 83.7% were white; mean age was 35.5 (SD 11.13) years; mean HS duration was 11.5 (SD 9.03) years. BL characteristics were similar between groups. 93.9% completed PerA. HiSCR rate at Wk12 was significantly higher for pts randomized to ADA (96/163, 58.9%) vs PBO (45/163, 27.6%; P \ .001). Statistically significant treatment differences were observed for all 3 ranked secondary endpoints (Wk12, ITT_A Population): 1) among pts with Hurley Stage II, significantly more ADA pts (44/85, 51.8%) achieved AN count of 0, 1 or 2 vs PBO (28/87, 32.2%; P ¼ .010); 2) significantly more ADA pts (48/105, 45.7%) achieved $30% reduction and $1 unit reduction from BL in Patients’ Global Assessment of Skin Pain numerical rating scale (NRS) based on 24hour recall of worst pain vs PBO (23/111, 20.7%; P \.001) among pts with BL NRS $3; 3) ADA pts achieved a significantly greater mean reduction from BL in modified Sartorius Score (n ¼ 163, -28.9) vs PBO (n ¼ 162, -9.5; P \.001). 57.7% (ADA) and 66.9% (PBO) reported $1 treatment-emergent adverse event (TEAE). TEAEs in $10% of pts in any treatment arm were headache (12.9% ADA; 12.9% PBO) and exacerbation of HS (4.3% ADA; 12.9% PBO). 1.8% (ADA) and 3.7% (PBO) had serious TEAEs. There were no deaths. Conclusions: Significantly more HS pts treated with ADA achieved clinically relevant reduction in objective disease activity and pain vs PBO. The safety profile for pts in both treatment groups was comparable. AbbVie Inc funded this study and participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing and approving of this publication. All authors had access to the data.
J AM ACAD DERMATOL
AB45
715
Differentiating confluent and reticulated papillomatosis from acanthosis nigricans Young Joon Park, MD, Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea; Sang Jin Kim, MD, Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea; Hee Young Kang, MD, PhD, Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea; Eun-So Lee, MD, PhD, Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea; You Chan Kim, MD, PhD, Department of Dermatology, Ajou University School of Medicine, Suwon, South Korea
Eczematous skin reaction after intravenous immunoglobulin (IVIG) therapy Jing Zhang, MD, Drexel Dermatology, Philadelphia, PA, United States; Carrie Ann Cusack, MD, Drexel Dermatology, Philadelphia, PA, United States
Background: Confluent and reticulated papillomatosis (CRP) is an uncommon dermatosis manifesting as papules that coalesce to form a reticular pattern. Because its histopathologic features are similar to those of benign acanthosis nigricans (bAN), differentiation between CRP and bAN can be challenging. Thus, we compared the clinicopathologic characteristics of CRP and bAN. Methods: We retrospectively reviewed 60 CRP and 30 AN patients. Clinical characteristics included age, sex, morphology, location, symptoms, associated conditions, duration, treatment, treatment response, and weight. Histologic examinations were conducted on 33 CRP and 30 AN lesions. Brown-Brenn Gram staining, periodic acid-Schiff (PAS) staining, and immunohistochemistry were used to identify relevant microorganisms or differential markers. Results: While CRP lesions were concentrated on the trunk, AN lesions also appeared in flexure areas, such as the axilla. The high prevalence of AN in obese subjects was consistent with previous studies. Increases in Ki-67 and keratin 16 expression did not differ significantly between CRP and AN lesions. CRP lesions did not show significant positivity compared to AN lesions with the PAS stain. Bacteria were detected at a higher rate in CRP lesions than in normal skin, with no difference between CRP and AN lesions. On Fontana-Masson and gp100 staining, pigmentation was significantly greater in AN lesions than in CRP lesions, showing more melanocytes. Conclusion: The location of skin lesions and BMI are the main clinical differentiating factors between CRP and AN. The epidermal histologic changes of CRP are milder than those of AN. AN also showed a greater degree of pigmentation and melanocytic proliferation. High detection rates of bacteria in the lesion-affected skin of CRP support the speculation that bacteria may play a role in the pathogenesis of CRP.
A 74-year-old Caucasian male with a medical history of stage 0 chronic lymphocytic leukemia (diagnosed 10/2010), stage T1c prostate cancer and chronic inflammatory demyelinating polyneuropathy undergoing IVIG therapy presented with a diffuse itchy rash that developed 3 hours after his sixth IVIG infusion. The eruption started on the upper chest and spread peripherally over several days. Two days after the eruption started, the patient went to the ED where he was prescribed prednisone along with clotrimazole cream topically without benefit. The patient otherwise reported his usual state of health. His other medications include aspirin, finasteride, losartan, omeprazole, simvastatin and tamsulosin. The patient’s physical examination revealed diffuse, confluent, scaling pink papules on the face, trunk, upper extremities and hands bilaterally. A biopsy from the right upper extremity was consistent with spongiotic dermatitis. The patient was diagnosed with an eczematous drug eruption secondary to IVIG and is being treated with topical steroids and oral antihistamines. He is now much improved. Intravenous immunoglobulin is increasingly utilized both on- and off-label for a host of conditions including dermatologic, neurologic, hematologic and immunologic disorders. This case highlights a potential adverse side effects from IVIG. Most side effects tend to be minor with about 30-40% of patients experiencing headaches, chills, fatigue, nausea, arthralgias, myalgias and back pain. In rare instances, serious reactions do occur, which include aseptic meningitis, renal failure, anaphylactic shock, hemolytic anemia and thrombosis. Cutaneous side effects from IVIG occur in only an estimated 0.4 - 6% of patients and range from localized to generalized eruptions. The reported reactions include vasculitis, urticaria, erythema multiforme, alopecia, lichenoid dermatitis, purpuric erythema and morbilliform eruptions. A newer and possibly underreported side effect is an eczematous eruption seen in our patient. It is important to be cognizant of this side effect in the practice of dermatology as it may be encountered with increasing frequency due to the expanding use of IVIG. Commercial support: None identified.
Commercial support: None identified.
631
1990 Diffuse dermal angiomatosis Aleta Simmons, MD, MS, University Hospitals/Case Western Reserve University, Cleveland, OH, United States; Pezhman Shoureshi, DO, University Hospitals/Case Western Reserve University, Cleveland, OH, United States; Kord Honda, MD, University Hospitals/Case Western Reserve University, Cleveland, OH, United States A 46-year-old woman with a history of recurrent bilateral anterior granulomatous uveitis treated with mycophenolate presented two weeks after a biopsy of the right breast for a suspicious growth. The surgical scar was intact but she noticed a gradual development of an enlarging, painful, nonhealing lesion surrounding the surgical scar. Examination revealed a linear surgical scar with an overlying ulcerated plaque with a hyperpigmented border on the right breast inferior to the nipple. An ANA panel was positive for La/SSB antibody. Histology revealed vascular proliferation composed of spindle-shaped endothelial cells with focal small blood vessel formation involving the superficial dermis and extending into deeper portions of the dermis focally, around adnexal structures, and dermal collagen bundles. Based on histology she was diagnosed with diffuse dermal angiomatosis (DDA). The patient improved with intralesional steroids and topical clobetasol. Prednisone was deferred due to her history of glaucoma. She has been taking pentoxifylline 400 mg orally three times a day without evidence of new lesions. DDA is a rare, benign, acquired condition characterized by diffuse proliferation of CD31 and CD34 positive endothelial cells within the dermis causing tender or painful plaques with central ulceration. Based on its histologic hallmark, it is classified as a cutaneous reactive angiomatosis. Clinically, the condition may resemble pyoderma gangrenosum when located near a surgical scar. Histologically, DDA may resemble Kaposi sarcoma, angiosarcoma, and acroangiodermatitis. DDA is associated with comorbidities that predispose patients to hypercoagulable states, such as hypertension, diabetes mellitus, peripheral artery disease, or cardiovascular disease. Smoking also contributes to development of the condition in these patients. The specific pathogenesis of DDA is unknown. DDA affects middle-aged female smokers with a history of vascular disease. Although, there was a case involving one male patient and two cases of patients without vascular disease. This patient is the first reported case involving a history of granulomatous uveitis and positive La/SSB antibodies. Treatment options include reversal of contributing factors including smoking cessation, weight loss, arterial stenting or bypass, reduction mammoplasty, initiation of antithrombotic medications such as aspirin and pentoxifylline, or starting isotretinoin which has a fibrinolytic effect. Commercial support: None identified.
MAY 2015
Efficacy and safety of adalimumab in patients with moderate to severe hidradenitis suppurativa: Results from PIONEER II, a phase 3, randomized, placebo-controlled trial Gregor Jemec, University of Copenhagen, Roskilde, Denmark; Alice Gottlieb, Tufts Medical Center, Boston, MA, United States; Seth Forman, Forward Clinical Trials, Tampa, FL, United States; Evangelos Giamarellos-Bourboulis, 4th Department of Internal Medicine, Athens, Greece; Ziad Reguiai, CHU de Reims, H^ opital Robert Debre, Service de Dermatologie, Reims Cedex, France; Yihua Gu, AbbVie Inc, North Chicago, IL, United States; Martin Okun, AbbVie Inc, North Chicago, IL, United States Introduction: PIONEER II evaluated the safety and efficacy of adalimumab (ADA) vs placebo (PBO) in patients (pts) with moderate to severe hidradenitis suppurativa (HS). Data from the first 12 weeks (wks) are reported. Methods: This multicenter study included a 12-wk double-blind PBO-controlled period (PerA). Pts were randomized 1:1 to blinded ADA 40mg weekly starting at Wk4 (following 160 mg at Wk0; 80 mg at Wk2) or matching PBO. At baseline (BL), pts had a diagnosis of HS for $1 year, a total abscess and inflammatory nodule (AN) count of $3, HS lesions in $2 body areas (1 at Hurley Stage II or III) and had no prior TNF-a inhibitor treatment. PerA efficacy was analyzed for all randomized pts (intentto-treat [ITT_A Population]); safety was analyzed for the ITT_A Population who received $1 dose of study drug. The primary endpoint was HiSCR (HS Clinical Response; $50% reduction from BL in AN count and no increase in abscess or in draining fistula counts) at Wk12. Results: Of the 326 in the ITT_A Population, 67.8% were women; 83.7% were white; mean age was 35.5 (SD 11.13) years; mean HS duration was 11.5 (SD 9.03) years. BL characteristics were similar between groups. 93.9% completed PerA. HiSCR rate at Wk12 was significantly higher for pts randomized to ADA (96/163, 58.9%) vs PBO (45/163, 27.6%; P \ .001). Statistically significant treatment differences were observed for all 3 ranked secondary endpoints (Wk12, ITT_A Population): 1) among pts with Hurley Stage II, significantly more ADA pts (44/85, 51.8%) achieved AN count of 0, 1 or 2 vs PBO (28/87, 32.2%; P ¼ .010); 2) significantly more ADA pts (48/105, 45.7%) achieved $30% reduction and $1 unit reduction from BL in Patients’ Global Assessment of Skin Pain numerical rating scale (NRS) based on 24hour recall of worst pain vs PBO (23/111, 20.7%; P \.001) among pts with BL NRS $3; 3) ADA pts achieved a significantly greater mean reduction from BL in modified Sartorius Score (n ¼ 163, -28.9) vs PBO (n ¼ 162, -9.5; P \.001). 57.7% (ADA) and 66.9% (PBO) reported $1 treatment-emergent adverse event (TEAE). TEAEs in $10% of pts in any treatment arm were headache (12.9% ADA; 12.9% PBO) and exacerbation of HS (4.3% ADA; 12.9% PBO). 1.8% (ADA) and 3.7% (PBO) had serious TEAEs. There were no deaths. Conclusions: Significantly more HS pts treated with ADA achieved clinically relevant reduction in objective disease activity and pain vs PBO. The safety profile for pts in both treatment groups was comparable. AbbVie Inc funded this study and participated in the study design; study research; collection, analysis and interpretation of data; and writing, reviewing and approving of this publication. All authors had access to the data.
J AM ACAD DERMATOL
AB45