Abstract
Dermatomyositis (DM) presents with inflammatory myopathy and distinct skin manifestations, often linked to specific autoantibodies. Anti-transcriptional intermediary factor-1 gamma (TIF-1γ) antibodies (Abs) are typically linked to DM in older patients and malignancy in 15% to 40% of cases. We highlight a case of a 24-year-old female who presented with weakness of proximal muscles, periorbital edema, heliotrope rash, erosions on oral mucosa, and painful scaly rash on the lower extremities. Transcriptional intermediary factor-1 gamma Abs were positive, confirming inflammatory myopathy. Treatment with steroid pulse therapy and immunoglobulin led to improvement. Evaluation for malignancy yielded unremarkable results. This case underscores the importance of recognizing and managing DM with TIF-1γ Ab positive, even in atypical demographics, and highlights the need for comprehensive malignancy evaluation.
Keywords
Background
Dermatomyositis (DM) is a rare autoimmune condition consisting of inflammatory myopathy and distinctive skin manifestations. Although DM usually manifests with weakness of proximal muscles and a skin rash, it includes a range of clinical phenotypes often linked to specific autoantibodies. Among these autoantibodies, transcriptional intermediary factor-1 gamma (TIF-1γ) antibodies (Abs) have emerged as markers for a distinct subset of DM, known for its association with malignancy and unique clinical features.
Dermatomyositis linked to anti-TIF-1γ Ab is characterized by Abs targeting TIF-1γ, a regulator of gene transcription and cellular differentiation. 1 This subtype is particularly notable for its association with cancer, especially among adult patients, with a reported incidence ranging from 15% to 40%. 2 The presence of TIF-1γ Abs has been associated with an increased risk of malignancy, particularly in the elderly and those with extensive cutaneous involvement and profound muscle weakness. 3
We highlight an intriguing case of a 24-year-old female who sought medical attention following a syncopal episode and was subsequently diagnosed with DM linked to TIF-1γ Ab. The patient’s age distinguishes this case, given that this condition is usually encountered in older individuals. This case underscores the importance of recognizing anti-TIF-1γ Ab positive DM as a separate clinical entity within the spectrum of DM, especially in young patients presenting with characteristic clinical features. The association with malignancy necessitates a comprehensive evaluation to exclude underlying neoplasms, emphasizing the importance of multidisciplinary management involving different specialists.
Case Presentation
A 24-year-old female with no notable medical history presented to the hospital after experiencing a syncopal episode followed by a fall. She denied any previous episodes of syncope. Her symptoms began 2 months ago with intermittent episodes of vomiting and dizziness lasting about 10 days, leading to hospitalization at another facility. During this time, she also experienced proximal muscle weakness, rendering her unable to lift herself from a chair or shower independently. In addition, she developed a scaly, non-pruritic but painful rash several months before admission, which initially appeared on her trunk and later progressed to involve her proximal bilateral upper and lower extremities. At the previous facility, she received treatment with topical emollients and steroids for the rash and was advised to undergo outpatient physical therapy, which temporarily improved her muscle weakness. However, 2 weeks before admission, she experienced a decline in muscle strength. Her family history was unremarkable except for cervical cancer in her grandmother.
Physical examination revealed periorbital edema, proximal muscle weakness in bilateral upper and lower extremities, heliotrope rash, erosions on oral mucosa (Figure 1), and rashes on bilateral lower extremities (Figure 2). Laboratory findings (Table 1) showed a hemoglobin level of 11.5 g/dL (normal = 10.9-14.3 g/dL), platelets 61 k/µL (normal = 150-450 K/µL), haptoglobin <8 mg/dL (normal = 30-250 mg/dL), lactate dehydrogenase (LDH) 752 U/L (normal = 110-260 U/L), immature platelet fraction 23.2% (normal = 0.8%-7.0%), reticulocyte count Abs 0.186 M/µL (normal = 0.023-0.094 M/µL), fibrinogen 466 mg/dL (normal = 214-454 mg/dL), D-dimer 2086 ng/mL (normal <500 ng/mL), prothrombin time (PT) 11.9 seconds (normal = 9.4-12.5 seconds), international normalized ratio (INR) 1.03, and activated partial thromboplastin time (aPTT) <21.0 seconds (normal = 25.1-36.5 seconds). The direct antiglobulin test was negative, and a peripheral smear revealed schistocytes. Creatinine kinase and aldolase levels were elevated to 604 U/L (normal = 20-180 U/L) and 10.2 U/L (normal = <7.7 U/L), respectively. Complement C3 and C4 levels were within normal range. The anti-nuclear Ab panel and vasculitis panel were negative. The myomarker panel was positive for TIF1-γ Abs with a level of 25 units (normal <20 units).
Ulceration noted on oral mucosa.
Reddish-purple rash on the lower extremity.
Laboratory Findings and Reference Ranges.
An magnetic resonance imaging (MRI) of the femur with Short Tau Inversion Recovery (STIR) sequence revealed diffuse myositis involving the bilateral thighs (Figure 3), prompting a muscle biopsy from the vastus lateralis, which confirmed findings consistent with inflammatory myopathy. A computed tomography (CT) chest ruled out interstitial lung disease (ILD) but identified pulmonary nodules in the right upper and right middle lobes, with the largest measuring 6 mm.
MRI of the femur with STIR sequence revealing diffuse myositis involving bilateral thighs.
The patient underwent 3 days of steroid pulse therapy and received 2 doses of intravenous immunoglobulin treatment. This resulted in symptomatic improvement, progressive enhancement in muscle strength, and resolution of the rash. She was initiated on 60 mg of prednisone, daily for maintenance therapy with a plan for tapering and subcutaneous methotrexate 10 mg weekly with folic acid supplementation.
Given anti-TIF-1γ Ab positive DM, the patient underwent evaluation for evidence of solid organ malignancy. A biopsy of the gastric mucosa during esophagogastroduodenoscopy (EGD) yielded unremarkable results, and an ultrasound of bilateral breasts showed no signs of malignancy. She continues to follow up with rheumatology as an outpatient.
Discussion and Conclusion
Dermatomyositis is a persistent inflammatory disease that impacts the skin and muscles. Adults between the ages of 50 and 60 years are usually affected, and most patients are female. There have also been reports of juvenile DM, which most commonly occurs between the ages of 5 and 15 years. 4 Clinically, this disease is marked by skeletal muscle weakness, primarily impacting the proximal muscles of the upper and lower extremities, along with skin manifestations.
Although DM is known to be an autoimmune condition, several new, targeted autoantibodies have recently been identified. 5 Antibodies linked to the onset of DM can be classified into myositis-specific Abs and myositis-associated Abs. 4 Myositis-specific autoantibodies have recently been used to classify inflammatory myopathy as each group has distinct features. 6 They include Abs against melanoma differentiation–associated gene 5 (MDA-5), anti-aminoacyl tRNA synthetase (ARS) such as anti-Jo-1 and anti-Mi-2.5,7,8 The MDA-5 Abs are commonly linked to clinically amyopathic DM. This condition may lead to clinical deterioration because of the rapid advancement of ILD, resulting in an unfavorable prognosis. 9
Autoantibodies targeting the specific aminoacyl transfer RNA (tRNA) synthetases are characteristic of anti-synthetase syndrome, an autoimmune condition that may present with symptoms such as myositis, non-erosive osteoarthritis, Raynaud’s phenomenon, and fever of unknown origin. The most widely recognized anti-synthetase Ab is anti-Jo-1, an anti-histidyl-tRNA synthetase. 10 Alternately, patients with DM linked to anti-TIF-1γ Ab, similar to our patient, commonly present with weakness of proximal muscles, skin rashes, and dysphagia. This type of DM typically does not involve ILD. 5 In addition, DM with positive anti-TIF-1γ Abs has been linked to cancer. 11
The likelihood of developing malignancy in cases of DM is 4.66 times greater as compared with the general population, and it is much higher in males and individuals older than 44 years. In the first year after being diagnosed with DM, there was a notably elevated risk of developing malignancy Systemic Inflammatory Reaction (SIR 17) recorded. 12 Patients with DM related to anti-TIF-1γ Ab have been reported to have a 19% to 100% incidence of cancer. 13 Best et al conducted a meta-analysis on 1962 DM patients, revealing that 22.2% of them tested positive for anti-TIF1-γ Abs. Moreover, the risk of cancer in these subjects was 9.37 times greater as compared with normal subjects. Regarding identifying malignancy in DM, the combined sensitivity and specificity of anti-TIF1-γ Abs were shown to be 52% and 92%, respectively. In individuals with anti-TIF1-γ Abs, solid tumors like ovarian, breast, lung, gastric, and colorectal cancers were also found to be more prevalent than hematological malignancies.14,15 Malignancy is usually detected in the 3 years following the diagnosis of DM, with most of them being detected in the first 12 months. 14
When it comes to the treatment of DM linked to anti-TIF-1γ Ab, the treatment of malignancies takes precedence. 5 Immunoglobulins, rituximab, and inhibitors of tumor necrosis factor-α demonstrate efficacy in patients with resistance to multiple drugs. Although corticosteroids prove effective for DM, instances of steroid resistance have been observed. In such cases, alternative non-steroidal medications like methotrexate, mycophenolate, azathioprine, and cyclosporine A may offer utility. Our patient required treatment with corticosteroids and intravenous immunoglobulins and was later started on subcutaneous methotrexate.16,17
Our case is unique as the patient is a young female with DM linked to anti-TIF-1γ Ab. According to studies, the mean age demonstrating positivity for anti-TIF-1γ Abs is 68.6 ± 10.7 years. 5 This is of clinical significance in 15% to 30% of adult cases diagnosed with DM as it can be the first symptom of undetected malignancy. In the case of breast cancer, TIF-1γ expression is linked to younger age, tumors bigger than 2 cm, higher malignant grade, and more estrogen receptor (ER) negativity. Moreover, TIF-1γ expression indicated a propensity for unfavorable outcomes. Early detection of anti-TIF-1γ Abs can expedite the diagnosis of DM associated with malignancy, enabling timely initiation of cancer treatment. 18
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding
The author(s) received no financial support for the research, authorship, and/or publication of this article.
Ethics Approval
Our institution does not require ethical approval to report individual cases or case series.
Informed Consent
Verbal informed consent was obtained from the patient(s) for their anonymized information to be published in this article.
