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Hydroxyurea-induced dermatomyositis-like eruption with abnormal expression of p53
P6183
P6517
Cutaneous ulceration: More than skin deep? Ruth Lamb, MBChB, Alan Lyell Centre for Dermatology, Glasgow, United Kingdom; Angela Drummond, MBChB, Alan Lyell Centre for Dermatology, Glasgow, United Kingdom; Sarah Digby, MBChB, Department of Pathology, Glasgow, United Kingdom; William Stewart, MBChB, Department of Neuropathology, Glasgow, United Kingdom
Hypomyopathic dermatomyositis with antibodies to MDA5 presenting with severe cardiomyopathy Ignasi Pau-Charles, MD, Department of Dermatology, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain; Adriana Garcia-Herrera, MD, Department of Pathology, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain; Jose M. Mascar o Jr, MD, Department of Dermatology, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain; Jose Maria Grau, MD, Departent of Internal Medicine, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain; Karem Ortiz, MD, Department of Dermatology, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain; Livia Casciola-Rosen, PhD, Division of Rheumatology, John Hopkins University School of Medicine, Baltimore, MD, United States; Pedro Castro, MD, Departent of Internal Medicine. Hospital Clınic, Universitat de Barcelona, Barcelona, Spain Melanoma differentiation-associated gene 5 (MDA-5) is a novel autoantigen that has been recently described in a subset of patients with hipo/amyopathic dermatomyositis (DM), and that is associated with a higher risk of interstitial lung disease. A 55-year-old Philippine man presented with a 7-month history of progressive asthenia, anorexia and 3 kg weight loss. He had recurrent episodes of bilateral and symmetrical polyarthralgia affecting his hands, elbows, shoulders, knees and feet, that were occasionally associated with low-grade fever and chill sensation. Over the last 3 months, he had also developed dyspnea to less than ordinary activity with orthopnea. Chest radiography showed a bilateral and diffuse interstitial fibrosis pattern, and an echocardiography demonstrated progressive heart failure and a severe pericardial effusion. Clinical examination revealed the presence of livedoid erythematoviolaceous macules affecting the palmar and dorsal aspects of the fingers of both hands, with several necrotic ulcers located around the fingertips. Small ulcerated papules were also present on the dorsal aspects of most metatarsophalangeal articulations. Prominent erythematous and hyperkeratotic plaques on the elbows and distal subungueal splinter hemorrhages on his hands were also noted. Cutaneous biopsies showed thrombosis and occlusion of arterioles, capillaries and small vessels in the medium and deep dermis, without associated inflammation. There was also prominent periadnexal mucin deposition in the deep reticular dermis and hypodermis. A muscular biopsy confirmed the diagnosis of DM. The patient was started on systemic corticosteroids, with mild overall improvement. Concomitant treatment with systemic azathioprine, cyclophosphamide and intravenous immunoglobulin was also added. Despite his slowly initial progressive improvement, his severe ventricular dysfuntion persisted. After being discharged from the ICU, the patient unexpectedly died from a third-degree atrioventricular block and electromechanical dissociation. A sample of the patient’s serum obtained premortem confirmed the presence of anti-MDA5 antibodies using immunoprecipitation techniques. In summary, we report the case of a patient with hypomyopathic anti-MDA5 positive DM with distinctive cutaneous findings and severe cardiac involvement, highlighting the importance of the dermatologist in identifying this particular cutaneous phenotype that may be a marker potentially severe form of DM.
Panniculitis is an immunologic and inflammatory disease of the subcutaneous tissues. Dermatomyositis is an acquired, chronic, inflammatory muscle disorder of unknown cause. To our knowledge, there have been 24 reported cases of dermatomyositis and panniculitis occurring concurrently in the same patient in the literature to date, and we report a further case in a 65-year-old Asian female. The patient, with biopsy-proven idiopathic panniculitis stable on treatment with low dose oral prednisolone, developed painful, ulcerated plaques over multiple joints and extensor surfaces, requiring high-dose oral prednisolone and hospital admission. Shortly after hospital admission, the patient developed proximal muscle weakness. A creatinine kinase level was found to be grossly elevated. Imaging, electromyogram, and muscle biopsy were in keeping with an idiopathic inflammatory myopathy, with histopathologic features highly suggestive of dermatomyositis. To date, this patient does not have the classical skin changes seen in dermatomyositis, such as Gottron papules and a heliotrope rash, in contrast to other reported cases. It is possible that these features are yet to develop or that the appearance of these signs was altered by the immunosuppression required for her other skin changes. Other differentials considered included immune myopathy with perimysial pathology (IMPP), which has similar pathology often without skin changes, however the case was felt to be most in keeping with dermatomyositis. The patient’s condition significantly improved on a combination of methotrexate and prednisolone, in keeping with other previous case reports. This case is also comparable to the other cases described in terms of the appearance and location of painful subcutaneous plaques. Accordingly, since panniculitis and dermatomyositis may coexist and are postulated to be part of the same disease process, consideration should be given to intermittently checking muscle enzymes in patients with chronic idiopathic panniculitis. In addition, without a systematic approach in this case, the myopathy could have been attributed to treatment with prednisolone thus delaying the diagnosis of dermatomyositis. This is most pertinent because of the lack of classical cutaneous features of dermatomyositis. Commercial support: None identified.
P6009 Hydroxyurea-induced dermatomyositis-like eruption with abnormal expression of p53 Blanca De Unamuno, MD, Hospital General Universitario de Valencia, Valencia, Spain; Juan Jose Vilata Corell, PhD, Hospital General Universitario de Valencia, Valencia, Spain; Rosa Ballester Sanchez, MD, Hospital General Universitario de Valencia, Valencia, Spain; Vıctor Alegre Miquel, PhD, Hospital General Universitario de Valencia, Valencia, Spain Background: Hydroxyurea (HU) is an antitumor agent used in the treatment of hematologic diseases. Up to 10% to 35% of patients in chronic treatment can develop cutaneous adverse effects, such as hyperpigmentation and xerosis. In addition, there have been described infrequent adverse effects, such as dermatomyositis-like eruption (DM-LE), HU-associated squamous dysplasia, and nonmelanoma skin cancers.
Commercial support: None identified.
Case report: A 76 year-old woman, diagnosed with idiopathic myelofibrosis and in treatment since 2004 with hydroxyurea. She was referred for evaluation of a skin rash on her dorsal hands, neck and face. Physical examination revealed erythematoviolaceous and scaly papules and plaques located over the metacarpophalangeal and proximal interphalangeal joints with periungual erythema. There was also erythema periorbital resembling ‘‘heliotrope erythema’’ and papules on her neck and front. Muscle examination yielded no abnormalities. Histopathologic examination of one of the violaceous plaques revealed an acanthotic epidermis, with hyperkeratosis, dyskeratosis, vacuolization of the basal layer, and an inflammatory lichenoid infiltrated in the dermoepidermic interface. It was also noted disorganization and queratinocitic atypia. Immunohistochemistry was performed and showed focal expression of p53 in dysplastic keratinocytes. HU was withdrawn and replaced with anagrelide. We observed gradual clinical improvement within 10 months. Conclusion: Chronic HU therapy has been associated DM-LE that presents as scaly erythematous patches, papules and plaques of the dorsal hands, and sometimes also with periorbital erythema. Patients rarely present other concomitant clinical or analytical significant alterations. Histologic analysis, which reveals an interface dermatitis with dyskeratotic keratinocytes and presence of mucin, does not aid in differentiating DM-LE from true DM. In addition to the DM-LE, it is well known the association between HU and the development of nonmelanoma skin cancer, which are usually squamous cell carcinomas. Sanchez-Palacios and Guitart proposed the term HU-associated squamous dysplasia (HUSD), as a premalignant precursor of aggressive squamous cell carcinomas, and identify the expression of p-53 along the basal cell layer of the epidermis. Subsequently, Kalajian et al presented a case of DMlike in which they also demonstrate the expression of p53 along the lower layers of the epidermis, thus demonstrating that it is also a premalignant precursor. Commercial support: None identified.
AB70
J AM ACAD DERMATOL
APRIL 2013
P6517
Cutaneous ulceration: More than skin deep? Ruth Lamb, MBChB, Alan Lyell Centre for Dermatology, Glasgow, United Kingdom; Angela Drummond, MBChB, Alan Lyell Centre for Dermatology, Glasgow, United Kingdom; Sarah Digby, MBChB, Department of Pathology, Glasgow, United Kingdom; William Stewart, MBChB, Department of Neuropathology, Glasgow, United Kingdom
Hypomyopathic dermatomyositis with antibodies to MDA5 presenting with severe cardiomyopathy Ignasi Pau-Charles, MD, Department of Dermatology, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain; Adriana Garcia-Herrera, MD, Department of Pathology, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain; Jose M. Mascar o Jr, MD, Department of Dermatology, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain; Jose Maria Grau, MD, Departent of Internal Medicine, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain; Karem Ortiz, MD, Department of Dermatology, Hospital Clınic, Universitat de Barcelona, Barcelona, Spain; Livia Casciola-Rosen, PhD, Division of Rheumatology, John Hopkins University School of Medicine, Baltimore, MD, United States; Pedro Castro, MD, Departent of Internal Medicine. Hospital Clınic, Universitat de Barcelona, Barcelona, Spain Melanoma differentiation-associated gene 5 (MDA-5) is a novel autoantigen that has been recently described in a subset of patients with hipo/amyopathic dermatomyositis (DM), and that is associated with a higher risk of interstitial lung disease. A 55-year-old Philippine man presented with a 7-month history of progressive asthenia, anorexia and 3 kg weight loss. He had recurrent episodes of bilateral and symmetrical polyarthralgia affecting his hands, elbows, shoulders, knees and feet, that were occasionally associated with low-grade fever and chill sensation. Over the last 3 months, he had also developed dyspnea to less than ordinary activity with orthopnea. Chest radiography showed a bilateral and diffuse interstitial fibrosis pattern, and an echocardiography demonstrated progressive heart failure and a severe pericardial effusion. Clinical examination revealed the presence of livedoid erythematoviolaceous macules affecting the palmar and dorsal aspects of the fingers of both hands, with several necrotic ulcers located around the fingertips. Small ulcerated papules were also present on the dorsal aspects of most metatarsophalangeal articulations. Prominent erythematous and hyperkeratotic plaques on the elbows and distal subungueal splinter hemorrhages on his hands were also noted. Cutaneous biopsies showed thrombosis and occlusion of arterioles, capillaries and small vessels in the medium and deep dermis, without associated inflammation. There was also prominent periadnexal mucin deposition in the deep reticular dermis and hypodermis. A muscular biopsy confirmed the diagnosis of DM. The patient was started on systemic corticosteroids, with mild overall improvement. Concomitant treatment with systemic azathioprine, cyclophosphamide and intravenous immunoglobulin was also added. Despite his slowly initial progressive improvement, his severe ventricular dysfuntion persisted. After being discharged from the ICU, the patient unexpectedly died from a third-degree atrioventricular block and electromechanical dissociation. A sample of the patient’s serum obtained premortem confirmed the presence of anti-MDA5 antibodies using immunoprecipitation techniques. In summary, we report the case of a patient with hypomyopathic anti-MDA5 positive DM with distinctive cutaneous findings and severe cardiac involvement, highlighting the importance of the dermatologist in identifying this particular cutaneous phenotype that may be a marker potentially severe form of DM.
Panniculitis is an immunologic and inflammatory disease of the subcutaneous tissues. Dermatomyositis is an acquired, chronic, inflammatory muscle disorder of unknown cause. To our knowledge, there have been 24 reported cases of dermatomyositis and panniculitis occurring concurrently in the same patient in the literature to date, and we report a further case in a 65-year-old Asian female. The patient, with biopsy-proven idiopathic panniculitis stable on treatment with low dose oral prednisolone, developed painful, ulcerated plaques over multiple joints and extensor surfaces, requiring high-dose oral prednisolone and hospital admission. Shortly after hospital admission, the patient developed proximal muscle weakness. A creatinine kinase level was found to be grossly elevated. Imaging, electromyogram, and muscle biopsy were in keeping with an idiopathic inflammatory myopathy, with histopathologic features highly suggestive of dermatomyositis. To date, this patient does not have the classical skin changes seen in dermatomyositis, such as Gottron papules and a heliotrope rash, in contrast to other reported cases. It is possible that these features are yet to develop or that the appearance of these signs was altered by the immunosuppression required for her other skin changes. Other differentials considered included immune myopathy with perimysial pathology (IMPP), which has similar pathology often without skin changes, however the case was felt to be most in keeping with dermatomyositis. The patient’s condition significantly improved on a combination of methotrexate and prednisolone, in keeping with other previous case reports. This case is also comparable to the other cases described in terms of the appearance and location of painful subcutaneous plaques. Accordingly, since panniculitis and dermatomyositis may coexist and are postulated to be part of the same disease process, consideration should be given to intermittently checking muscle enzymes in patients with chronic idiopathic panniculitis. In addition, without a systematic approach in this case, the myopathy could have been attributed to treatment with prednisolone thus delaying the diagnosis of dermatomyositis. This is most pertinent because of the lack of classical cutaneous features of dermatomyositis. Commercial support: None identified.
P6009 Hydroxyurea-induced dermatomyositis-like eruption with abnormal expression of p53 Blanca De Unamuno, MD, Hospital General Universitario de Valencia, Valencia, Spain; Juan Jose Vilata Corell, PhD, Hospital General Universitario de Valencia, Valencia, Spain; Rosa Ballester Sanchez, MD, Hospital General Universitario de Valencia, Valencia, Spain; Vıctor Alegre Miquel, PhD, Hospital General Universitario de Valencia, Valencia, Spain Background: Hydroxyurea (HU) is an antitumor agent used in the treatment of hematologic diseases. Up to 10% to 35% of patients in chronic treatment can develop cutaneous adverse effects, such as hyperpigmentation and xerosis. In addition, there have been described infrequent adverse effects, such as dermatomyositis-like eruption (DM-LE), HU-associated squamous dysplasia, and nonmelanoma skin cancers.
Commercial support: None identified.
Case report: A 76 year-old woman, diagnosed with idiopathic myelofibrosis and in treatment since 2004 with hydroxyurea. She was referred for evaluation of a skin rash on her dorsal hands, neck and face. Physical examination revealed erythematoviolaceous and scaly papules and plaques located over the metacarpophalangeal and proximal interphalangeal joints with periungual erythema. There was also erythema periorbital resembling ‘‘heliotrope erythema’’ and papules on her neck and front. Muscle examination yielded no abnormalities. Histopathologic examination of one of the violaceous plaques revealed an acanthotic epidermis, with hyperkeratosis, dyskeratosis, vacuolization of the basal layer, and an inflammatory lichenoid infiltrated in the dermoepidermic interface. It was also noted disorganization and queratinocitic atypia. Immunohistochemistry was performed and showed focal expression of p53 in dysplastic keratinocytes. HU was withdrawn and replaced with anagrelide. We observed gradual clinical improvement within 10 months. Conclusion: Chronic HU therapy has been associated DM-LE that presents as scaly erythematous patches, papules and plaques of the dorsal hands, and sometimes also with periorbital erythema. Patients rarely present other concomitant clinical or analytical significant alterations. Histologic analysis, which reveals an interface dermatitis with dyskeratotic keratinocytes and presence of mucin, does not aid in differentiating DM-LE from true DM. In addition to the DM-LE, it is well known the association between HU and the development of nonmelanoma skin cancer, which are usually squamous cell carcinomas. Sanchez-Palacios and Guitart proposed the term HU-associated squamous dysplasia (HUSD), as a premalignant precursor of aggressive squamous cell carcinomas, and identify the expression of p-53 along the basal cell layer of the epidermis. Subsequently, Kalajian et al presented a case of DMlike in which they also demonstrate the expression of p53 along the lower layers of the epidermis, thus demonstrating that it is also a premalignant precursor. Commercial support: None identified.
AB70
J AM ACAD DERMATOL
APRIL 2013