Two recent investigations by Cleveland Clinic researchers are providing insights into the treatment and complications of the inflammatory, immune-mediated skin and muscle disorder dermatomyositis (DM).
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One study adds new information about treatment response and malignancy-associated clinical features in patients with clinically amyopathic dermatomyositis (CADM) — a poorly characterized subtype of dermatomyositis that generally lacks muscle involvement and for which cutaneous disease is the predominant clinical feature. Previous research has suggested a link between CADM and various cancers.
In the second study, Cleveland Clinic researchers documented that intravenous immunoglobulin (IVIG) can be an effective treatment for dystrophic calcinosis, which is the abnormal deposition of calcium in skin, muscle and/or subcutaneous tissue in some dermatomyositis patients.
The results of the investigation of CADM prompted the researchers to recommend careful screening for, and aggressive treatment of, the condition. The researchers also found evidence suggestive of distinct idiopathic CADM and malignancy-associated CADM pathophysiologies.
“The concept of clinically amyopathic dermatomyositis as a subtype of dermatomyositis has only been around for several decades,” says Anthony P. Fernandez, MD, PhD, Director of Medical Dermatology in the departments of Dermatology and Anatomic Pathology at Cleveland Clinic and senior author of both studies. “We wanted to improve the characterization of this condition — in terms of underlying malignancies and outcomes — so we can better understand how to treat it.”
The need for aggressive treatment
In the CADM study, published in the British Journal of Dermatology, Dr. Fernandez and colleagues conducted a retrospective review of 44 Cleveland Clinic patients diagnosed with the disorder and whose medical records contained clinical and serologic data prior to the start of treatment. Of those patients treated with first-line prednisone alone (n = 25), the researchers found that 80 percent showed initial improvement in cutaneous symptoms. However, most of these patients (88 percent) eventually required additional systemic treatment within six months of diagnosis.
“The importance of our study is that we showed that dermatologists should not be fooled by initial skin improvements in clinically amyopathic dermatomyositis patients who receive only prednisone as a first-line treatment,” Dr. Fernandez says. “Treating these patients conservatively does not work. In order to get the disease under control, most patients will require a corticosteroid plus another steroid-sparing immunosuppressant medication such as methotrexate.”
The hands of a 66-year-old female patient exhibit Gottron papules — one of three major cutaneous criteria, along with biopsy consistent with cutaneous dermatomyositis and absence of myositis with six months of skin disease onset, that are required for the diagnosis of clinically amyopathic dermatomyositis. Copyrighted photo from Galimberti F, Li Y, Fernandez AP. Clinically amyopathic dermatomyositis: clinical features, response to medications and malignancy-associated risk factors in a specific tertiary-care-centre cohort. Br J Dermatol. 2016 Jan;174(1):158-164. Used with permission from John Wiley & Sons, Inc.
Documenting CADM-associated malignancies
The risk of cancer in patients with classic DM is well-known, but the connection between CADM and malignancies is less clear. The Cleveland Clinic researchers found that 14 percent of their CADM study cohort developed associated malignancies within five years of CADM diagnosis, including two patients who were diagnosed with Merkel cell carcinoma, a rare and aggressive skin cancer not previously linked to DM.
Previously documented clinical indicators of malignancy in classic DM were not confirmed in the CADM cohort, and periungual erythema, which has been found to be associated with malignancy in DM, seemed to be protective against malignancy in the CADM study’s patients. The clinical differences, along with absence of most autoimmune antibodies and a more likely response to first-line treatment in the malignancy-associated CADM patients compared with the non-malignancy-associated CADM patients, led the authors to suggest that malignant CADM is a true subtype of classic DM, with potential pathophysiological differences from idiopathic CADM.
In addition, the possible link between CADM and Merkel cell carcinoma underscores the need for healthcare professionals to perform a full skin examination at the time of diagnosis and at each follow-up visit, the researchers conclude.
Assessing IVIG’s impact on calcinosis
In the second study, Dr. Fernandez and colleagues assessed the efficacy of IVIG to treat calcinosis cutis, a complication that most frequently occurs in pediatric patients with juvenile dermatomyositis. Dermatomyositis-associated calcinosis is difficult to treat and causes significant morbidity, including contracture, skin necrosis and pain. “Some patients have pain with every movement because of calcinosis cutis, or they can’t sit down because of the amount of calcium deposition in the skin of their buttocks,” Dr. Fernandez says. “There is a significant unmet medical need for a good treatment.”
In the study, published in the Journal of the American Academy of Dermatology, the Cleveland Clinic researchers reviewed the charts of 249 patients diagnosed with dermatomyositis who had at least two clinically recorded episodes since 2004 and who also had sufficient medical data to retrospectively confirm the diagnosis. The investigators identified eight patients whose dermatomyositis-associated calcinosis had not responded to at least two systemic medications prior to starting IVIG therapy.
Disease response was assessed six to 12 months after starting IVIG and was defined as being either “improved” or “stable/worse.” Calcinosis symptoms clinically improved in five patients treated with IVIG; three patients had stable or worsening calcinosis following treatment. All patients whose calcinosis responded to IVIG also experienced cutaneous and musculoskeletal symptom improvement.
However, the study’s small sample size (N = 8) and lack of objective evidence of improvement means the results are insufficient to justify recommending IVIG for calcinosis treatment, Dr. Fernandez says. The symptom assessments were based solely on treating clinicians’ visual observations before and after IVIG treatment and were not supplemented with objective evaluations made through measurements or imaging of calcium deposits, Dr. Fernandez explains.
He and his colleagues plan to continue studying IVIG treatment for dermatomyositis-associated calcinosis by measuring calcium deposits before and after therapy to more objectively assess disease response, he says.
“The study is not strong enough by itself to support any definitive conclusions about the effectiveness of IVIG treatment for calcinosis,” Dr. Fernandez says. “But, we at least saw a positive correlation, so we can say that we should be cognizant of IVIG as a potential treatment for calcinosis — particularly if we are already thinking about IVIG as a systemic treatment for the patient’s dermatomyositis.”