Question

A 79-year-old gentleman presented to the ED with altered mental status. The day prior, his family had found him “confused and weak” which resolved by later that evening. However, the next day, he was “dazed” had difficulty walking, which sparked the presentation to the emergency room. On examination, the patient was found to have an erythematous to violaceous, somewhat reticulated plaque on the posterior neck with a background of mottled, reddish-brown patches (figure 1). On the left hand, he was found to have eroded erythematous papules of the MCPs, PIPs, DIPs and in between the joint spaces (figure 2).

Based on the most likely diagnosis, which of the following would not be a reasonable part of the work up in adult patients?

1. Pulmonary function tests
2. CA 19-9
3. CT chest/abdomen/pelvis
4. MRI brain
5. EKG/echocardiogram

Correct Answer

Correct Answer: (4) MRI brain

Explanation

Poikiloderma of the neck, with classic “Gottron’s papules” on the left hand, are most concerning for a diagnosis of dermatomyositis. Dermatomyositis (DM) is an idiopathic multi-system inflammatory condition that is of presumed autoimmune pathogenesis¹ . It classically presents with a symmetric, proximal, extensor inflammatory myopathy and a characteristic cutaneous eruption. Dermatomyositis has a bimodal age distribution, with both adult and juvenile forms. The pathogenesis is believed to be a result of an immune mediated process triggered by external factors (malignancy, infectious agents) in genetically predisposed individuals¹ . Additionally, the interferon pathway has recently been implicated as critical in its pathophysiology² . Serum antinuclear autoantibodies are often present which further supports an autoimmune etiology.

The cutaneous features include pathognomonic findings of Gottron’s papules (pink to violaceous papules on dorsal hands) and heliotrope eruption (pink-violaceous erythema involving the upper eyelids). Other findings include poikiloderma of the upper back (“shawl” sign) and upper chest, nailfold abnormalities (periungal erythema, dilated capillary nail bed loops) as well as scaly erythema of the lateral thighs (holster sign) and scalp involvement³ . In juvenile DM, calcinosis cutis is common, particular on the extensor surfaces¹ . When evaluating muscle disease, a detailed history assessing proximal muscle groups as well as strength testing should be performed. Cutaneous disease precedes the appearance of myositis by 3-6 months in almost 50% of cases while 10% have myositis prior to any skin findings³ . Importantly, DM exists on a spectrum where either skin or muscle phenotype can predominate and can also present as amyopathic. Diagnosis is often made clinically without a skin biopsy however it may be helpful if exam findings are subtle or atypical.

Histopathology shows an interface dermatitis with dermal mucin deposition, which would be indistinguishable from lupus erythematosus³. Myositis specific autoantibodies in recent years have been helpful in identifying associated phenotypes. Anti-Mi-2 is associated with both adult and juvenile DM, with milder muscle disease and a good response to treatment¹. Anti-MDA5 is associated with rapidly progressive interstitial lung disease and cutaneous ulcerations³. Anti-TIF-1 gamma and Anti-NXP-2 are most closely associated with malignancy³. Once DM is diagnosed, additional work up is required including but not limited to serum CK/aldolase, EMG or MRI of muscle, pulmonary function tests (answer choice 1), EKG/echocardiogram (answer choice 5) and barium swallow or manometry¹. Dermatomyositis and its association with malignancy is well known, with a recent study showing the risk to be 6x higher than the general population⁴.

Most common malignancies include ovarian, colon, breast, lung, hematopoietic and nasopharyngeal cancer, particularly in Asian populations⁵. Although no specific guidelines exist, initial work up includes CBC, CMP and UA as well as chest x-ray and age-appropriates screening. CT chest/abdomen/pelvis (answer choice C) is typically performed if the initial work up is worrisome or in patients that are considered high risk. CA 125 and CA 19-9 (answer choice B) can be considered based on individual patient risk factors. Brain MRI (answer choice D) is not routinely part of the work up as brain neoplasms/malignancies are not strongly associated with DM. Treatment includes skin directed therapy with topical steroids, calcineurin inhibitors and photoprotection¹. Historically for patients with severe disease, first line therapy included systemic steroids plus disease modifying antirheumatic drugs such as methotrexate, azathioprine, or mycophenolate mofetil². However, IVIG was recently FDA approved for DM and has shown to be very effective regardless of disease severity6. Rituximab or cyclophosphamide are sometimes added, particularly when there is lung or severe muscle involvement⁷. Apremilast has been shown to help with recalcitrant disease and can be considered as an adjunct treatment⁸. JAK inhibitors as well as more targeted therapy (anti-IFN antibodies) will likely play a more substantial role in the future ^9,10

Incorrect answer choices (choice 1) – Pulmonary complications are a well-known cause of morbidity and mortality in dermatomyositis and are a critical part of the work up. (choice 2) – CA19-9 screens for pancreatic cancer and is sometimes indicated as part of the work up based on patient risk factors. (choice 3) – CT chest/abdomen/pelvis is often indicated in adult patients to evaluate for malignancy. (choice 5) – EKG or echocardiogram is performed as conduction defects or other arrhythmias can be seen and do not always present with symptoms.

References

1. Bolognia, J., Schaffer, J., & Cerroni, L. (2018). Dermatology (Fourth edition.). Philadelphia,Pa: Elsevier. 2. Bolko L, Jiang W, Tawara N, Landon-Cardinal O, Anquetil C, Benveniste O, Allenbach Y. The role of interferons type I, II and III in myositis: A review. Brain Pathol. 2021 May;31(3):e12955. doi: 10.1111/bpa.12955. PMID: 34043262; PMCID: PMC8412069. 3. Cobos GA, Femia A, Vleugels RA. Dermatomyositis: An Update on Diagnosis and Treatment. Am J Clin Dermatol. 2020 Jun;21(3):339-353. doi: 10.1007/s40257-020-00502-6. PMID: 32096127. 4. Hu T, Vinik O. Dermatomyositis and malignancy. Can Fam Physician. 2019 Jun;65(6):409-411. PMID: 31189628; PMCID: PMC6738379. 5. Leatham H, Schadt C, Chisolm S, Fretwell D, Chung L, Callen JP, Fiorentino D. Evidence supports blind screening for internal malignancy in dermatomyositis: Data from 2 large US dermatology cohorts. Medicine (Baltimore). 2018 Jan;97(2):e9639. doi: 10.1097/MD.0000000000009639. PMID: 29480875; PMCID: PMC5943873. 6. Werth VP, Aggarwal R, Charles-Schoeman C, Schessl J, Levine T, Kopasz N, Worm M, Bata-Csörgő Z. Efficacy of intravenous immunoglobulins (IVIg) in improving skin symptoms in patients with dermatomyositis: a post-hoc analysis of the ProDERM study. EClinicalMedicine. 2023 Oct 2;64:102234. doi: 10.1016/j.eclinm.2023.102234. PMID: 37799613; PMCID: PMC10550512. 7. UpToDate. (n.d.). Retrieved April 10,2024, from https://www.uptodate.com/contents/diagnosis-and-differential-diagnosis-of-dermatomyositis-and-polymyositis-in-adults. 8. Bitar C, Ninh T, Brag K, Foutouhi S, Radosta S, Meyers J, Baddoo M, Liu D, Stumpf B, Harms PW, Saba NS, Boh E. Apremilast in Recalcitrant Cutaneous Dermatomyositis: A Nonrandomized Controlled Trial. JAMA Dermatol. 2022 Dec 1;158(12):1357-1366. doi: 10.1001/jamadermatol.2022.3917. PMID: 36197661; PMCID: PMC9535502. 9. Paik JJ, Lubin G, Gromatzky A, Mudd PN Jr, Ponda MP, Christopher-Stine L. Use of Janus kinase inhibitors in dermatomyositis: a systematic literature review. Clin Exp Rheumatol. 2023 Mar;41(2):348-358. doi: 10.55563/clinexprheumatol/hxin6o. Epub 2022 Jun 28. PMID: 35766013; PMCID: PMC10105327. 10. Aggarwal, R., Domyslawska, I., Carreira, P., Fiorentino, D., Sluzevich, J., Werth, V., Banerjee, A., Chu, M., Oemar, B., Salganik, M., Sloan, A., Vincent, M., & Peeva, E. (2023, June 1). POS1207 efficacy and safety of ANTI-IFNΒ-SPECIFIC monoclonal antibody, PF-06823859, on myositis: Phase 2 study in patients with moderate-to-severe dermatomyositis. Annals of the Rheumatic Diseases. https://ard.bmj.com/content/82/Suppl_1/936.1.citation-tools