Anti-SAE1 Antibodies and Dermatomyositis: A Case Series of Three Patients

Diagnosing clinically amyopathic dermatomyositis (CADM) is a challenge for clinicians due to the lack of classic muscle findings associated with dermatomyositis (DM) and the wide array of clinical presentations depending on the associated antibody subtype. In 2007, Betteridge et al. described a new subtype of CADM associated with Anti-small ubiquitin-like modifier activating enzyme 1(anti-SAE1) antibodies. This subtype of CADM is often recalcitrant to treatment and may be associated with severe cutaneous disease, dysphagia, and interstitial lung disease. To date, few patients with anti-SAE1 DM have been described, and usually in large descriptive cohort studies including all DM subtypes. Thus, it is increasingly important to further describe this rare subtype to solidify cutaneous findings, associated symptoms, and potential therapeutic options. Herein, we describe three patients with anti-SAE1 DM, with one patient presenting with a previously undescribed cutaneous manifestation.

trunk, and upper extremities (Figure 1).At presentation, patient did not report any myalgias, weakness, dysphagia, dyspnea, or weight loss. Over the next several months, patient developed muscle weakness and dysphagia, which responded to a combination of monthly intravenous immune globulin (IVIg), mycophenolate mofetil (MMF), and prednisone. However, her cutaneous disease did not improve with the above treatments in addition or to intramuscular and topical corticosteroids and worsened with hydroxychloroquine, which was then discontinued.

Case 2
A 57-year-old African American woman presented with a 1.5 month history of lesions clinically consistent with discoid lupus erythematosus (DLE) (Figure 2). The patient denied myalgias, weakness, or dyspnea. Hydroxychloroquine resolved her eroded DLE-like lesions, with multiple areas of scarring left behind.
Three months later, she developed extensive violaceous, erythematous, and edematous macules, papules, patches, and plaques on the face, neck, chest, arms, dorsal hands, and lateral thighs consistent with a diagnosis of dermatomyositis. She was subsequently hospitalized due to severe dysphagia, which improved with intravenous methylprednisolone. Methotrexate, oral corticosteroids, and topical corticosteroids were started in addition to hydroxychloroquine with no significant improvement in cutaneous manifestations.

Case 3
A 66-year-old woman presented with over a one-year history of a diffuse pruritic, burning erythematous eruption covering the face, trunk, upper extremities, and knees ( Figure  3). On presentation, patient reported no myalgias, dysphagia, dyspnea, or weight loss.
However, over time, the patient developed generalized weakness, which improved (along with cutaneous findings) with topical and oral corticosteroids and MMF.
Histopathology for all three cases demonstrated a vacuolar interface dermatitis with stromal mucin deposition and nonspecific direct immunofluorescence findings. Additionally, a dermatomyositis panel was positive for anti-SAE1 antibodies for all three patients. Table 1  Myositis typically develops several months after the onset of skin findings in this specific patient population, with elevated creatinine kinase (CK) levels being very common. 3 Elevated CK levels among these patients have been noted by Peterson et al. 4/5 patients with elevated CK. Among the Asian cohorts, the Fujimoto study found 5/7 patients with elevated CK. 3 Within our small cohort, CK and aldolase levels were initially all within normal limits, however, CK levels became elevated in Cases 1 and 2. Case 3 did develop severe subjective weakness despite normal CK. Furthermore, two of our three patients were ANA positive, with one patient demonstrating anti-histone antibodies, and another with anti-ssDNA antibodies, findings not described in the literature with respect to this specific subset of DM patients.
Two of the three patients developed CT findings consistent with interstitial lung disease, another commonly reported finding among this patient population. This report supports this complicating feature in anti-SAE1 patients. To date, none of our patients have been diagnosed with a malignancy, which aligns with other studies. 3 Of our three patients, Case 2 deviated the most from all reported cases with respect to cutaneous findings. Though ulcerations have been reported in dermatomyositis, a case of diffuse eroded plaques has not been reported in the onset of DM in the literature. Though her initial cutaneous ulcerations improved with hydroxychloroquine and prednisone, the diffuse poikilodermatous erythroderma that later developed did not. Rituximab infusions have also not been beneficial for Case 2.
Furthermore, Case 3 showed very good response to the addition of MMF with oral steroids, with remarkable improvement in her cutaneous disease and muscular weakness. Case 1 showed improvement in Finally, a majority of DM cases are considered idiopathic, but cases of medication induced dermatomyositis have been reported. 6 It is important to note that two of our three patients were on statin medications prior to the development of skin disease. Unfortunately, their disease persisted despite discontinuation of this medication, and statin involvement should be considered in each case of DM.
Limitations of this study include our small sample size of three patients. This limits the generalizability of our results. Therefore, it is important that more case-series limited to this specific subtype be published to help identify clinical features and possible treatments.
Herein, we add three patients to the literature with this uncommon subtype of CADM. Additionally, we demonstrate several key clinical and laboratory findings that deviate from the average phenotype of CADM patients with anti-SAE1 antibodies.