Diagnosis of Thyroid Neoplasm-Associated Dermatomyositis in Ethiopian Woman

Introduction

Dermatomyositis (DM) is a rare autoimmune disease (inflammatory muscle disease) characterized by inflammatory injury of skeletal muscles and progressive symmetrical, predominantly proximal muscle weakness and skin rash.¹ Patients with dermatomyositis usually present with violaceus or dusky skin rash on faces and knuckles and proximal, symmetrical muscle weakness.² Males and females are equally affected, with a prevalence of 1 in 100,000 for both.³ Around 30% of dermatomyositis cases are associated with malignancy. It can sometimes present as para-neoplastic manifestation of malignancy.⁴ Different case series and population-based studies have estimated that diagnosis of concomitant malignancy among DM patients varies from 15% to 27%, with increasing percentages as age increases.^4,5 This paper aimed to present a case of thyroid neoplasm-associated dermatomyositis with a significant clinical response, particularly in the skin, following treatment with prednisolone and methotrexate.

Case Presentation

A 52-year-old female patient from Wolkiet (Northwest Ethiopia) was apparently healthy two years ago but then started experiencing irritability, heat intolerance and diaphoresis. She had an anterior neck swelling of 30 years’ duration. For this, she was evaluated at Haider referral hospital (North Ethiopia), diagnosed with a toxic multinodular goiter and managed with propylthiouracil 100 mg orally (po) three times per day. Six months following initiation of the medication, her symptoms improved, and she was offered surgical treatment, which she refused. Four months prior to her current presentation, she developed generalized body fatigue which worsened during activities like climbing stairs, combing her hair and standing from a squatting position. Concomitantly, she noticed violaceous rash over both hands and neck, which later involved the anterior part of her bilateral thighs and shoulders, hair loss and facial puffiness, but no morning stiffness. One week preceding her current visit, she had difficulty swallowing food, and was unable to support her head. On physical examination, she was acutely sick looking, conscious and oriented. Vital signs were all in normal ranges (blood pressure [BP] = 110/80 mmHg; pulse rate [PR] = 88 beats/minute; respiratory rate [RR] = 24 breaths/minute; temperature [T^oc] = 36.7°^C; Sa02 = 94% while breathing in room air). She had pink conjunctivae and non-icteric sclera. The anterior neck mass measured 4 by 5 cm, and was non-tender, mobile, multi-nodular, hard in consistency, not attached to overlying skin and showed no palpable lymphadenopathy. The chest was resonant on percussion note and clear on auscultation. Heart sounds were well heard, and there was no murmur or gallop. Abdominal examination revealed no enlarged organ or any sign of fluid collection and she had no visible deformity or limitation of movement on locomotor examination. As shown in Figure 1, on integumentary examination, there was an erythematous hyper-pigmented lesion on her face with periorbital edema (heliotrope rashes) (A); confluent violaceous and erythematous macular rashes on the knuckles of the hands (Gottron’s sign) (B) and macular rashes on the forearms with a salt and pepper appearance (C); and violaceous macular rashes on the neck line (V-shaped rashes) (D), shoulder and back (shawl’s sign) (E) and upper thighs, laterally (holster sign) (F). Additionally, she had a hypopigmented area on her nails, hands, anterior chest and bilateral thigh. On neurologic examination, she was alert and oriented to time, place and person, and cranial nerves were all intact. She had difficulty holding objects against gravity and standing from a squatting position. Sensory examination was normal and meningeal irritation signs were absent. Her laboratory test results (see Table 1) showed that she had moderate anemia (hemoglobin = 10.9g/dl, MCV = 78.0 Fl, and RDW: 13.5%), with normal other blood cell lines and erythrocyte sedimentation rate. Liver enzyme was mildly elevated (SGOT/AST: 52.97IU/L SGPT/ALT: 52.99IU/L), and serum albumin was low (2.6g/dl) with a normal bilirubin level. Renal function tests and serum electrolytes were normal. Thyroid function tests were within normal range. Urine analysis and serology test results were unremarkable. Serum creatine kinase before treatment was mildly elevated = 232u/l (normal range =20 – 198). The results of serology tests, such as the ANA, RF and anti-HIV antibody were non-revealing. Another immunological panel was not done due to limited clinical set up (Table 1).

Table 1 Laboratory Profile of Dermatomyositis in a Thyroid Cancer Patient at University of Gondar Hospital

Figure 1 Skin manifestation dermatomyositis in thyroid cancer patient at University of Gondar Hospital during admission. (A) skin manifestation on face (heliotrope rash), (B) Gutron’s papule, (C) skin manifestation on hand, (D) V-sign, (E) shawl’s sign, (F) holster sign.

Thyroid FNAC smears showed cellular aspirate composed of moderately pleomorphic round to polygonal cells admixed with scant colloid suggestive of thyroid follicular neoplasm. Thyroid gland biopsy was not possible since excision is required. Thyroid ultrasound showed multiple hyper-echoic masses on the left side of the thyroid measuring 4.5×2.4 cm, with calcification and multiple ipsilateral neck lymphadenopathy, the largest measuring 1.2 cm on the short axis dimension suggestive of thyroid malignancy. Chest x-ray was normal. Muscle biopsy showed increased nuclear internalization, scattered lymphocyte infiltration and atrophy, which was suggestive of inflammatory myopathy (see Figure 2).

Figure 2 Muscle biopsy of dermatomyositis in thyroid cancer patient at University of Gondar Hospital.

The diagnosis of thyroid neoplasm-associated dermatomyositis was considered based on ACR-EULAR classification criteria⁶ and the patient was put on prednisolone 40mg daily, methotrexate 7.5 mg po weekly, folic acid 5 mg po daily and cotrimoxazole 960 mg po 3 times per week. Broad spectrum sunscreen and liquid paraffin (moisturizer) were applied on a daily basis. The patient was advised on regular exercise, avoidance of direct sunlight exposure and was linked to chronic follow-up clinic. After 2 weeks of steroid treatment, the patient showed remarkable improvement in muscle strength, and the steroid dose was tapered every week thereafter. After 2 months of treatment, she showed dermatological improvement and her physical exercise endurance was also significantly better, as shown in Figure 3.

Figure 3 Skin manifestation of dermatomyositis in thyroid cancer patient at University of Gondar Hospital (ffter 2 months of treatment). (A) skin manifestation on face (heliotrope rash), (B) Gutron’s papule, (C) V-sign, (D) holster sign.

Discussion

Dermatomyositis is an idiopathic inflammatory myopathy typically characterized by differential muscle weakness (predominantly proximal muscles) and skin rashes. The degree of muscle and skin involvement varies from patient to patient. Some patients may have no muscle weakness while others may have minimal or diffuse muscle weakness.⁷ More than 85% of dermatomyositis patients with muscle weakness have elevated serum creatinine kinase levels.⁸ In a dermatomyositis suspected patient, detailed evaluation of their history and a physical examination emphasizing skin inspection and assessment of muscle strength are necessary. Patients should be assessed for indicators of severe disease, including cardiorespiratory symptoms and dysphagia requiring early airway support.⁹ Most dermatomyositis patients present at clinics with a complaint of proximal muscle weakness, which includes symptoms like difficulty arising from a chair, climbing stairs, lifting objects, or washing hair. Symptoms of distal muscle weakness like difficulty holding and manipulating objects may occur later. In most severe forms of the disease the extensor neck muscles and proximal esophagus muscles can be involved, and patients can present with an inability to support their head, dysphagia, dysphonia, and weakness in respiratory muscles, as seen in our patient.¹⁰ The peculiar skin manifestations of dermatomyositis can occur before, alongside or shortly after muscle weakness. The commonest cutaneous manifestations of dermatomyositis include the heliotrope eruption, midfacial erythema that involves the nasolabial folds, Gottron papules, Gottron sign, poikilodermatous changes, dilated capillaries, and dropout of capillaries within the proximal nail folds, cuticular hypertrophy, and nonscarring alopecia often with diffuse erythema and scaling.¹¹ The prevalence of malignancy in dermatomyositis patients is as high as 17.2%.¹² The commonest malignancies associated with dermatomyositis include nasopharyngeal, lung, breast, ovarian, and hematologic cancers.^13,14 There are also case reports of dermatomyositis associated with thyroid cancer patients, of which papillary thyroid cancer is the commonest.^15,16 Though there are data discrepancies, it is reported that underlying malignancy is higher in those who have constitutional symptoms, absence of Raynaud's phenomenon, elevated erythrocyte sedimentation rate, and severe form of disease.¹⁷ In dermatomyositis patients, screening for cancer is controversial, and requires shared decision-making methods in order to determine whether malignancy screening is valuable.^4,12

Although there is no cure for dermatomyositis, there are treatment options that can improve skin manifestations and muscle strength. Prednisone 1 mg/kg per day with a broad spectrum sunscreen is the initial treatment choice, improving symptoms within 4 weeks of treatment initiation.^10,18 Following clinical response, the steriod dose should be tapered by 1mg/kg every other day for 10 weeks.¹⁹ If prednisolone is not clinically suitable, either methotrexate or azathioprine can suffice. Biological agents like rituximab, and intravenous immunoglobulin (IVIG) are options for those who are unresponsive to standard therapy.²⁰

Conclusion

A high index of clinical suspicion is required for early diagnosis of dermatomyositis in resource-limited settings to improve patient outcomes and identify associated co-morbidities.