Dermatomyositis (DM) and its Relation to Malignancies

Abstract

A patient presented to the primary office with regular complains of arthralgia and weakness and experienced a unique combination of conditions, cascading events that presented a therapeutic and diagnostic observation that explained a previously misunderstood clinical condition and response. Reviewing and analyzing patient’s data with clinical preceptor revealed possible relation of dermatomyositis to cancer/malignancy and prompted a clinical question “Can dermatomyositis increase a person’s risk for malignancy?”. PubMed, CINAHL and manual search was performed from 2014-2019 using terms “dermatomyositis”, “cancer”, and “malignancy” for related to this case study and clinical question literature. Literature review were synthesized and utilized in the case study to resolve a clinical question. Revealed pertinent to this case data from literature review clearly emphasized that patients with dermatomyositis have high incidence of cancer and should be evaluated by performing systematic screening or workup for possible malignancy.

Keywords:  Dermatomyositis, related, malignancy, between, cancer, review, risk.

Introduction

The rationale to choose this case was a unique combination of conditions and cascading events that presented a therapeutic and diagnostic observation that explained a previously misunderstood clinical condition and response. The study presents a 78 years old gentleman who developed different symptoms of dermatomyositis (DM was not recognized at that time) and was treated for those symptoms as they came, on separate occasions at different times before he was diagnosed with DM, and two months later developed prostate cancer (Ca). The purpose of the paper would be to try to find out if there is relationship between DM and Ca/malignancies. The patient had multiple encounters in primary care and dermatologist offices that followed initial complains, and in-patient admission to the hospital where he was diagnosed with DM and prostate CA. The patient had Medicare at the time of encounters and his insurance plan was able to cover the cost of his visits to medical offices, hospitalization and medications needs.

To transform nursing education and prepare new advance practice nurses to address developing needs of the health care system, The Essentials of Master’s Education in Nursing were developed. The following Essentials of Master’s Education in Nursing that could be applied to presented patient’s encounters information were identified as: I – Background for Practice from Sciences and Humanities; VII – Interprofessional collaboration for improving Patient and Population Health Outcomes, and IX – Master’s-Level Nursing Practice (AACN, 2011).

Case History

The patient initially presented to his primary care physician (PCP) with neck pain and weakness. Lab work was drawn, and the patient was referred to physical therapy to improve his pain and build up some strength. AST/ALT elevations were found when results were back, and Lipitor was discontinued. Another encounter was in PCP office two weeks later for facial rash and patient was referred to dermatologist. After little while the patient was admitted inpatient to the hospital for worsening severe proximal muscle weakness. Lab results showed: CK 8372, ANA 1:2560, negative ENA, EMG positive for “active myopathy with denervation in proximal muscles”. Muscle biopsy was done, patient was treated with Prednisone 60 mg/day for active myopathy and discharged. Muscle biopsy returned positive for anti-MI-2 with inflammatory myopathy and the patient was re-admitted to the hospital for worsening proximal weakness, dysphagia, CK 5189, troponin 3.4. Hospital rheumatologist identified heliotrope and Gottron’s papules on exam, the patient was diagnosed with DM (ICD-10 M33.10) and short-term mechanical ventilation during hospital stay. The patient was treated with pulse steroids following with prednisone 60mg per day orally. Normally, high-dose daily oral corticosteroids would be used as the first-line therapy and pulse dose intravenous methylprednisolone (IVMP) has been used for serious or returned/repeated cases (Raghu, Manadan, Schmukler, Mathur & Block, 2015). While hospitalized, the patient developed hematuria and urinary tract infection due to traumatic insertion of Foley catheter because of history of benign prostatic hyperplasia (BPH) and was treated and followed by urologist.

During follow up visits with urologist the patient was diagnosed with prostate Ca (ICD-10 C61) and treated with implanted radioactive seeds. High dose rate (HDR) brachytherapy is reported as a safe and effective local treatment for prostate Ca (Demanes & Ghilezan, 2014). The patient felt surprised with cancer diagnosis because he knew he had a history of BPH but did not expect it to turn to a cancer. Patient’s other medical history included bacteremia, balanoposthitis, bladder calculus, hypertension, herpes simplex encephalitis, hyperlipidemia, nephrolithiasis, phimosis. The patient is only allergic to lidocaine that caused swelling of the site and has no other, environmental or food allergies. The patient has no pertinent to the case family history. He is retired, widowed, sexually not active, lives with his daughter and she is durable power of attorney. Another social history would include no tobacco, alcohol or illicit drugs use. The patient is trying to: eat healthy (includes vegetables and fruits to his diet), walk and exercise everyday as tolerated, wears seat belt in the car.

On examination, patient presents pleasant and cooperative. Stated had difficulty performing some daily activities on his own. His muscle strength has remained good while at rehab and the patient continues his prednisone taper. He can transfer on his own and walk with assistance. No muscle pain, no joint pain, no recurrent skin rash. He denies any other significant complains. No reported fever, chills, night sweats, chest pain, palpitations, any swellings. No reported shortness of breath or cough. Weight has been stable, and appetite has been good. No skin issues noted on physical exam and other parts of the physical exam was unremarkable and were not pertinent to this case study. The patient was told to follow up scheduled appointments with urologist and PCP and call the office if he feels getting sick or having rash or any pain back.

Clinical question

Simple complains and symptoms that the patient came to PCP office with initially gradually turned to the serious medical condition that required patient’s hospitalization. The patient came with arthralgia and muscle weakness and in less than a year eventually was diagnosed with DM and prostate CA. It was surprising to find out that the patient was found and diagnosed with prostate Ca even knowing that he has a history of BPH because it was monitored by urologist in the office on the regular basis and it was no concerns raised at that time. Discussion with student’s preceptor revealed possible relation of DM to prostate Ca as well as to different forms of cancers and prompted the clinical question: “Can dermatomyositis increase a person’s risk for malignancy?”

Literature review

A literature review of DM and its relation to malignancy was performed by utilizing different strategies. One of the searching strategies to identify and select related to this case study data included using manual search on Google Scholar. Other searching strategies to perform literature review included utilizing different databases, such as: PubMed and CINAHL. Key words: “DM, related, malignancy, cancer, review, risk” were used for Google Scholar and search results were limited by applying following filters: custom range (from 2014), include patents, include citations and 10 articles were read from received data and three articles with words “malignancy, DM, cancer, related, review, risk” were selected and listed for this study case (see Table1: Literature review in Appendix). PubMed search results with key words “DM, related, malignancy, between” showed total of 1811 available articles (hits). The search was narrowed with “2014 - present year” filter to 348 results. After “clinical trial, reviews, full text, humans” filters/limiters were applied results were narrowed down to 64 articles. Ten articles with word “DM” in their title were selected for more detailed evaluation. Four articles were found appropriate for literature review as related to this case study (see Table1: l Literature review in Appendix). Search results with key words “DM, risk, cancer” in CINAHL database revealed total of 49 articles. Words AND, AND NOT, OR were also used to improve search and to receive more concentrated results. One relevant to this case study article was identified after search was limited to “full text, evidenced based practice, peer reviewed, 2014-2019 range” (see Table1: Literature review in Appendix). Total of seven articles were identified and used for this literature review (listed in Table 1). All listed articles were kept because authors of all of them acknowledged relationship between DM and malignancy. One article suggested that risk of malignancy should be considered in adult DM patients (Muro et al., 2015). One article suggested that risk for malignancy is significant within the 5 years after diagnosis (De Greef et al., 2018). One article suggested to monitor signs of DM because it may cause development or return existed malignancy (Adi et al., 2015). Remaining four other articles (listed in Table 1) suggested that patients with DM would have high incidence/increased risk/higher rate/greater risk of cancer or malignancies (Gkegkes, Minis & Iavazzo, 2018; Qiang, Kim, Baibergenova & Alhusayen, 2017; Iaccarino et al., 2014; Olazagasti, Baez, Wetter & Ernste, 2015). Another common similarity in all listed articles is treatment of DM with steroids (starting with high dose) and surgical removal of malignancy if/when it develops.

Discussion

This case study was able to disclose a close relationship between DM and malignancies.

 A lot of similarities was found in reviewed articles in terms of patient’s clinical presentation of DM and its most common symptoms described as proximal muscle weakness, skin lesions, Gottron’s papules and Heliotrope rash. DM is usually defined as an inflammatory myopathy of unknown cause and mechanism of this myopathy followed by malignancy is still not clear (Park, Pyo, Park, Lee, SK. & Lee, SW., 2014). It was interesting to discover that Anti-Mi-2 antibody is correlated with classical DM and is the most frequent myositis specific antibody (MSA) found in patients with DM (Iaccarino et al., 2014). Patient presented in this case study was positive for Anti-Mi-2 antibody and it just confirmed his diagnosis of DM and a few months later he was diagnosed with prostate Ca. This fact could logically lead to the conclusion that the patient developed prostate malignancy as a direct result of previously diagnosed DM, but there is not enough data to support this statement. This would be a limitation for this review, as a lack of enough randomized control trials, systematic reviews or meta-analyses to prove that the patient in this case study developed prostate Ca because of been previously diagnosed with DM. Only one article was found from 2006 (earliest) that presented a case of prostate Ca possibly associated with patient’s DM. At present, very limited number of cases (total of nine from 2002-04, 2000, 1996, 1978, 1971, 1970, 1968) was found in medical literature that reported association of DM with prostate Ca (Mooney, Dunphy, Stone & McNeel, 2006). This inconclusive data will not allow to state that the patient presented in this case study developed prostate malignancy as the result of being pre-diagnosed with DM. However, a literature review reveals significant amount of data that allows to answer clinical question “Can dermatomyositis increase a person’s risk for malignancy?” with the answer “yes”. The overall potential to develop cancer of unknown primary (CUP) was increased among patients with DM (Hemminki, Sundquist, Sundquist, & Ji, 2015). Patients with DM have higher probability to develop malignancy than normal patients. In patients with DM malignancies develop in 30% of cases with higher incidence in men and older people. The potential for cancer is higher during the first year of diagnosis and exists for both genders in all ages with DM. These DM patients would have elevated risk for common types of cancers such as: ovarian, gastric, lungs, non-Hodgkin’s and colorectal malignancies (Iaccarino et al, 2014; Qiang et al., 2017). Retrospective cohort study showed a correlation in 36% of the 104 patients who were diagnosed with different types of cancers within approximately seven days of confirmation of DM (Park et al., 2014). Like classic DM, ovarian and nasopharyngeal cancers are also common in amyopathic dermatomyositis (Udkoff & Cohen, 2016). Other limitations for this study due to lack of information in included articles would be risk factors variables such as smoking .and alcohol and literature searches were limited to English language articles.

Conclusion

This case is a unique combination of conditions and cascading events that presented a therapeutic and diagnostic observation that explained a previously misunderstood clinical condition and response. From simple initial complaints and symptoms patient’s condition turned into DM and prostate Ca diagnoses for the patient. Making referral to physical therapy, consulting with dermatologist, collaborating with hospital team – these are this case study’s examples of Essential VII. Literature review confirmed that DM significantly increases risk of different forms of cancer. Understanding significance of this increased risk is eminently pertinent in helping health care providers in their clinical decision making, such as systematic diagnostic workup for malignancy (Olazagasti et al, 2015). Integrating screening for cancer based on the results of scientific findings would be an example of Essential I: Background for Practice from Science and Humanities. Future studies that needed to support the practice of malignancies screening and keeping in mind the need to screen for malignancy in patients with DM (Qiang et al., 2017). The Essential IX can be summarized in this last sentence of presented case study – screening for cancer is essential when making a diagnosis of dermatomyositis (De Greef et al., 2018).

References

• Adi, A. H., Alturkmani, H., Spock, T., Williams Yohannes, P., Wargo, S., Szabo, E., Gutkind, J. S. and Van, Waes, C. (2015). Dermatomyositis paraneoplastic syndrome before symptomatic tonsillar squamous cell carcinoma: A case report. Head Neck, 37: E1-E3. doi:10.1002/hed.23703
• American Association of Colleges of Nursing. (2011). The essentials of master’s education innursing. Retrieved from http://www.aacn.nche.edu/education-resources/MastersEssentials11.pdf (Year). Article Title. Journal Title, Pages From - To.
• De Greef A, Marot L, Yildiz H, et al. (2018). Dermatomyositis with anti-TIF1-γ antibodies. BMJ Journals. Case Reports. Vol.2018: bcr-2018-227574. Retrieved from: http://dx.doi.org/10.1136/bcr-2018-227574
• Demanes, J. & Ghilezan, M. (2014). High-dose-rate brachytherapy as monotherapy for prostate cancer. Elsevier Inc. Brachytherapy, Vol.13,529-541. Retrieved from: https://doi.org/10.1016/j.brachy.2014.03.002
• Gkegkes, ID., Minis, EE., Iavazzo, C. (2018). Dermatomyositis and colorectal cancer: a systematic review. Ir J Med Sci, Vol.Aug;187(3):615-620. doi: 10.1007/s11845-017-1716-7. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/29168152
• Hemminki, K., Sundquist, K., Sundquist, J. and Ji, J. (2015), Risk of cancer of unknown primary after hospitalization for autoimmune diseases. Int. J. Cancer, 137: 2885-2895. doi:10.1002/ijc.29657
• Iaccarino, L., Ghirardello, A., Bettio, S., Zen, M., Gatto, M., Punzi, L. & Doria, A. (2014). The clinical features, diagnosis and classification of dermatomyositis. Journal of Autoimmunity, Vol.48–49, pp.122-127. Retrieved from: https://doi.org/10.1016/j.jaut.2013.11.005
• Mooney, C. J., Dunphy, E. J., Stone, B. and McNeel, D. G. (2006), Identification of autoantibodies elicited in a patient with prostate cancer presenting as dermatomyositis. International Journal of Urology, 13: 211-217. doi:10.1111/j.1442-2042.2006.01263.x
• Muro, Y., Sugiura, K., Nara, M., Sakamoto, I., Suzuki, N., Akiyama, M. (2015). High incidence of cancer in anti-small ubiquitin-like modifier activating enzyme antibody-positive dermatomyositis. Rheumatology,Vol.54(9), pp.1745-1747. doi.org/10.1093/rheumatology/kev247
• Olazagasti, J., Baez, P., Wetter, D., & Ernste, F. (2015). Cancer Risk in Dermatomyositis: A Meta-Analysis of Cohort Studies. American Journal of Clinical Dermatology, 16(2), 89–98. https://doi-org.proxy.library.ohio.edu/10.1007/s40257-015-0120-1
• Park, JS., Pyo, JY., Park, YB., Lee, SK., Lee, SW. (2014). Dermatomyositis Associated with Gallbladder Cancer. J Rheum Dis. Vol. Oct;21(5):261-265. Retrieved from: https://doi.org/10.4078/jrd.2014.21.5.261
• Qiang, JK., Kim, WB., Baibergenova, A., Alhusayen, R. (2017). Risk of Malignancy in Dermatomyositis and Polymyositis. J Cutan Med Surg, Vol.Mar/Apr;21(2):131-136. doi: 10.1177/1203475416665601. Retrieved from: https://www.ncbi.nlm.nih.gov/pubmed/27534779
• Raghu, P., Manadan, A., Schmukler, J., Mathur, T. & Block, J. (2015). Pulse Dose Methylprednisolone Therapy for Adult Idiopathic Inflammatory Myopathy. American Journal of Therapeutics, Vol.22(4), pp.244–247.doi: 10.1097/MJT.0000000000000175
• Udkoff, J. & Cohen, PR. (2016). Amyopathic Dermatomyositis: A Concise Review of Clinical Manifestations and Associated Malignancies. Am J Clin Dermatol. Vol.Oct;17(5):509-518. DOI: 10.1007/s40257-016-0199-z

Appendix

Table 1

Literature review