Cutaneous Manifestations of Systemic Disease — Clinical Case

DCE Long Case

Patient profile

Mrs R is a 63-year-old retired teacher who presents to her general practitioner with a three-month history of progressive difficulty climbing stairs, lifting groceries and swallowing solid foods, accompanied by a rash on her face and hands. ^[1]

Presenting concern: Over three months Mrs R has noticed progressive weakness in her proximal muscles — difficulty rising from a chair, climbing stairs and lifting her arms to wash her hair. Over the past six weeks she has had dysphagia to solids with occasional regurgitation. A violaceous rash appeared on her upper eyelids and over her knuckles, has spread to her chest and the back of her shoulders, and is worsened by sun exposure. She has lost 5 kilograms. She has no chest pain, palpitations, or change in bowel habit. She has not noticed any vaginal bleeding or discharge. ^[1]

Past medical history: Hypertension (well controlled on amlodipine 5 mg daily). Cholecystectomy at age 45. No history of malignancy, autoimmune disease or chronic skin disease. Menopause at age 52. No previous colonoscopy or mammography screening abnormality. ^[1]

Medications: Amlodipine 5 mg daily, no over-the-counter medications or supplements. No new medications in the past year. ^[1]

Family history: Mother had breast cancer at age 70. Father had ischaemic heart disease. One sister with hypothyroidism. No known family history of ovarian, gastric or colorectal cancer. ^[1]

Social: Lives with her husband. Two adult children. Never smoked. Alcohol 2 to 4 standard drinks per week. Independent in activities of daily living until this illness. ^[1]

Examination:

• Alert, orientated, comfortable at rest. Temperature 36.8. Pulse 78 regular. Blood pressure 132 over 82. Respiratory rate 16. SpO2 98 per cent room air.
• Skin: Heliotrope rash — violaceous erythema with oedema of the upper eyelids. Gottron papules — violaceous papules over the MCP and PIP joints of both hands. Periungual erythema with ragged cuticles (Samitz sign). Dilated nailfold capillary loops on inspection with a magnifying loupe. Photosensitive violaceous erythema over the anterior chest in a V distribution (V sign) and the posterior neck and shoulders (shawl sign). No oral ulcers, no livedo, no palpable purpura, no erythema nodosum.
• Neurological: Power 4 over 5 in shoulder abduction and hip flexion bilaterally (proximal weakness). Distal power 5 over 5. Reflexes present and symmetrical. Sensation intact. Bulbar: palatal lift reduced, cough on attempted water swallow (concerning for aspiration).
• Respiratory: Vesicular breath sounds, no crackles. FVC at the bedside 1.6 litres (approximately 65 per cent of predicted).
• Cardiovascular: Dual heart sounds, no murmur, no rub.
• Abdomen: Soft, non-tender. No organomegaly. No masses palpable.
• Pelvic: To be performed by gynaecology. ^[1]

Investigations:

• Haemoglobin 118 g per litre (normocytic); white cell count 7.2; platelets 320. ESR 42 mm per hour. CRP 6 mg per litre (normal).
• Creatine kinase 4800 U per litre (markedly elevated). Aldolase elevated. AST 120, ALT 60 (of muscle origin).
• Renal and liver function otherwise normal. Glucose 5.2. TSH normal.
• ANA positive at 1:160 (homogeneous). Anti-dsDNA negative. Anti-Smith negative. Complements normal.
• Myositis antibody panel: anti-TIF1-gamma positive. Anti-Jo-1 negative. Anti-Mi-2 negative. Anti-NXP-2 negative.
• High-resolution CT of the chest: no interstitial lung disease. Lung function: FVC 65 per cent of predicted, reduced maximum inspiratory and expiratory pressures consistent with mild respiratory muscle weakness. DLCO mildly reduced.
• CT chest abdomen pelvis: a complex right adnexal mass measuring 6 by 5 centimetres with solid and cystic components and a small volume of ascites. No hepatic metastases. No lymphadenopathy.
• Serum CA-125: 480 U per millilitre (markedly elevated).
• Pelvic ultrasound: the right adnexal mass is complex with internal vascularity and septations, suspicious for malignancy. ^[1]

Candidate's opening statement (SASPOP)

"This is Mrs R, a 63-year-old retired teacher presenting with anti-TIF1-gamma positive adult-onset dermatomyositis as a paraneoplastic marker of a presumed ovarian malignancy. Over three months she has developed progressive proximal muscle weakness with a creatine kinase of 4800, dysphagia to solids with an aspiration risk, and the pathognomonic cutaneous features of dermatomyositis — a heliotrope rash, Gottron papules, periungual changes and the photosensitive V and shawl signs. Her CT chest abdomen pelvis performed as part of the structured malignancy search has revealed a complex right adnexal mass measuring 6 by 5 centimetres with ascites, and her CA-125 is 480. Her anti-TIF1-gamma positivity places her in the highest-risk subgroup for paraneoplastic disease, and ovarian cancer is the classic association in women. Her main problems are: (1) paraneoplastic dermatomyositis with significant proximal myositis and dysphagia carrying an aspiration risk; (2) a presumed ovarian malignancy requiring urgent gynaecological oncology evaluation; (3) mild respiratory muscle weakness with an FVC of 65 per cent of predicted, which needs monitoring; (4) the cutaneous disease, which is photosensitive and distressing; and (5) the psychosocial impact of a new diagnosis of both a muscle disease and a cancer. My priorities are to commence immediate high-dose immunosuppression for the myositis while simultaneously arranging urgent gynaecological oncology evaluation of the ovarian mass, to protect her swallow and respiratory function with speech pathology and serial lung function, and to coordinate a multidisciplinary plan." ^[1]

Structured problem list (numbered, prioritised)

1. Anti-TIF1-gamma positive adult-onset dermatomyositis as a paraneoplastic marker of presumed ovarian malignancy — the overarching integrating diagnosis; mandates simultaneous immunosuppression and malignancy search.
2. Significant proximal myositis (CK 4800) with dysphagia and aspiration risk — requires immediate immunosuppression and swallow assessment.
3. Mild respiratory muscle weakness (FVC 65 per cent of predicted) — needs monitoring, may progress, risk of type 2 respiratory failure.
4. Presumed ovarian malignancy (complex adnexal mass with ascites, CA-125 480) — requires urgent gynaecological oncology referral for staging and surgical management.
5. Photosensitive cutaneous disease — requires sun protection and topical measures while systemic therapy takes effect.
6. Hypertension — continue amlodipine, monitor with the steroid therapy.
7. Psychosocial impact — the new diagnosis of a muscle disease and a cancer in a previously well woman; requires multidisciplinary support. ^[1]

Integrated management plan

Step 1 — Immediate immunosuppression for the dermatomyositis: ^[1]

Mrs R has significant myositis and dysphagia, with a high creatine kinase and an aspiration risk. I would commence: ^[1]

• Oral prednisone 0.5 to 1 mg per kg per day (approximately 40 to 60 mg daily), with a proton pump inhibitor, bone protection (calcium and vitamin D, and a bisphosphonate if indicated by FRAX and bone density), and pneumocystis prophylaxis with trimethoprim-sulfamethoxazole given the moderate-dose steroids and likely immunosuppressive.
• A steroid-sparing agent — my preference is methotrexate (10 mg once weekly with folate, titrating to 20 to 25 mg) or azathioprine (1 to 2 mg per kg per day, checking thiopurine methyltransferase first), to allow earlier steroid taper. Intravenous immunoglobulin (2 g per kg per month in divided doses) has good evidence in dermatomyositis with dysphagia and would be a strong consideration given her bulbar involvement.
• Monitoring — serial creatine kinase and aldolase, symptom assessment (dysphagia, proximal strength), and skin examination. The target is a falling creatine kinase toward normal, improved strength and resolution of the dysphagia. I would expect a response within 4 to 8 weeks. ^[1]

Step 2 — Protect the swallow and respiratory function: ^[1]

• Speech pathology review of swallow safety, with a modified barium swallow or fibreoptic endoscopic evaluation of swallow. Given the cough on the bedside water swallow, I would make her nil by mouth pending the swallow assessment, maintain hydration with intravenous fluids, and consider nasogastric feeding if the swallow is unsafe.
• Serial lung function — FVC at least weekly during admission, and maximum inspiratory and expiratory pressures. An FVC below 60 per cent of predicted or a falling trend would escalate to non-invasive ventilation (BiPAP) and intensification of the immunosuppression (intravenous methylprednisolone, intravenous immunoglobulin, rituximab for refractory disease).
• Aspiration precautions — head of bed elevated, careful oral hygiene, and a low threshold for chest X-ray and broad-spectrum antibiotics if any signs of aspiration pneumonia. ^[1]

Step 3 — Urgent gynaecological oncology referral: ^[1]

The complex adnexal mass with ascites and a CA-125 of 480 is highly suspicious for ovarian malignancy, and this is the paraneoplastic driver of her dermatomyositis. I would refer urgently to gynaecological oncology for: ^[1]

• Staging imaging — an MRI pelvis to characterise the mass, and a CT or PET-CT to complete staging.
• Tumour markers — CA-125 (already elevated), CEA, and other markers as guided by the oncology team.
• Surgical planning — staging laparotomy or laparoscopy with total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy, peritoneal biopsies and debulking, depending on the staging and histology. The principle is that treating the ovarian cancer often improves the dermatomyositis. ^[1]

Step 4 — Complete the structured malignancy search: ^[1]

Even though the ovarian mass is the most likely paraneoplastic driver, the principle with anti-TIF1-gamma positive dermatomyositis is to be systematic. I would complete the age-appropriate screen with: ^[1]

• Mammography — given her family history of breast cancer.
• Upper and lower gastrointestinal endoscopy — to exclude gastric, colorectal and pancreatic primaries, which are also classic paraneoplastic associations.
• Review of any other symptoms — and targeted investigation as guided by the history and examination. ^[1]

Step 5 — Manage the cutaneous disease: ^[1]

• Sun protection — broad-spectrum sunscreen, protective clothing, avoidance of peak sun, given the photosensitivity of the dermatomyositis rash.
• Topical corticosteroids and moisturisers — for symptomatic relief of the rash.
• The cutaneous disease typically responds to the systemic immunosuppression over weeks to months. ^[1]

Step 6 — Supportive and preventive care: ^[1]

• Physiotherapy for the proximal weakness, with a graded program as the myositis comes under control.
• Dietitian input for the swallow-restricted diet and nutritional support.
• Psychology and social work for the emotional and practical impact of a new diagnosis of both a muscle disease and a cancer. ^[1]

Step 7 — Communication, follow-up and safety: ^[1]

I would sit with Mrs R and her husband, with the rheumatology nurse specialist, the gynaecological oncologist, and a palliative care or supportive care liaison as appropriate. I would explain that her rash and muscle weakness are part of a condition called dermatomyositis, that this condition is sometimes linked to an underlying cancer, that the CT scan has found an ovarian mass that is likely to be the trigger, and that treating the ovarian cancer often improves the muscle and skin disease. I would explain the treatment plan in phases — the immediate immunosuppression for the myositis, the swallow and respiratory assessment to keep her safe, the gynaecological oncology plan for the ovarian cancer, and the longer-term follow-up. I would be honest that the next few months will be demanding, that the prognosis depends on the stage and histology of the ovarian cancer and the response of the myositis, and that the team will coordinate care and keep her informed. I would arrange close follow-up with serial bloods and lung function during admission, and document the shared decisions. ^[1]

Probing questions the examiner would ask

Q: She develops a fever and a productive cough on day 5 of her admission. How do you respond? ^[1]

A: "The first question is whether this is aspiration pneumonia, opportunistic infection from the immunosuppression, or community-acquired pneumonia. She has dysphagia with an aspiration risk, she is on moderate-dose corticosteroids and likely a steroid-sparing agent, and she is in hospital. My approach is a full septic screen — blood cultures, sputum culture, chest X-ray, arterial blood gas if hypoxic, and a urinary culture — and empiric broad-spectrum antibiotics covering community-acquired and aspiration pathogens (for example, ceftriaxone plus metronidazole, or piperacillin-tazobactam, guided by local guidelines and allergy). I would hold further escalation of her immunosuppression until infection is treated, continue her current steroid dose (do not stop steroids abruptly in an immunosuppressed patient as this risks adrenal crisis), and involve infectious diseases if the infection is severe or opportunistic (Pneumocystis, CMV, fungal). The principle is that infection is more common than a disease flare in an immunosuppressed patient, and empiric escalation of immunosuppression in the setting of untreated sepsis can be fatal." ^[1]

Q: How would you counsel her on the prognosis of her dermatomyositis and its relationship to the ovarian cancer? ^[1]

A: "I would be honest and hopeful in equal measure. The dermatomyositis is a paraneoplastic phenomenon — the immune response against the ovarian cancer is cross-reacting with her muscle and skin. The good news is that paraneoplastic dermatomyositis often improves substantially when the underlying tumour is treated; the muscle weakness, dysphagia and rash can resolve or greatly improve after surgical resection of the ovarian cancer, in parallel with the immunosuppression. The prognosis of the dermatomyositis itself is therefore tied to the prognosis of the ovarian cancer — which depends on the stage and histology and the response to surgery and chemotherapy. I would explain that the next steps are the gynaecological oncology evaluation and the staging, and that we will have a clearer picture then. I would emphasise that the immunosuppression is controlling the muscle disease in the interim, that we are protecting her swallow and respiratory function, and that the multidisciplinary team will coordinate her care. I would offer psychology and cancer support services and arrange follow-up with clear safety-netting for any new symptoms." ^[1]

Q: Her FVC falls to 55 per cent of predicted on day 4. What is your management? ^[1]

A: "This is respiratory muscle weakness progressing to the threshold for ventilatory support. An FVC below 60 per cent of predicted in dermatomyositis is an indication for non-invasive ventilation, both to unload the fatiguing respiratory muscles and to prevent overnight hypoventilation. I would: ^[1]

First, escalate the immunosuppression. I would move from oral prednisone to intravenous methylprednisolone (500 to 1000 mg daily for 3 days), and add intravenous immunoglobulin at 2 g per kg per month in divided doses, which has good evidence in dermatomyositis with respiratory involvement. Rituximab is a rational option in refractory disease. ^[1]

Second, commence non-invasive ventilation (BiPAP), titrated to clinical response and blood gases, with close monitoring on a high-dependency or intensive care unit. ^[1]

Third, monitor blood gases and serial FVC; if she progresses to hypercapnic respiratory failure despite non-invasive support, she may need intubation and mechanical ventilation. The prognosis in that situation is guarded and would prompt a goals-of-care discussion with Mrs R and her family, taking into account the paraneoplastic context and the ovarian cancer. ^[1]

Fourth, continue the aspiration precautions and the gynaecological oncology plan in parallel — treating the underlying cancer is the most effective treatment for the paraneoplastic myositis." ^[1]

Q: What is the mechanism by which the ovarian cancer triggers the dermatomyositis? ^[1]

A: "The leading hypothesis is that paraneoplastic dermatomyositis is the result of antigenic cross-reactivity between the tumour and regenerating muscle. The tumour expresses antigens (which may include proteins normally expressed only in fetal or regenerating muscle) that trigger a T-cell and antibody-mediated immune response. This response cross-reacts with regenerating muscle fibres, activating complement and producing a microangiopathy of the muscle capillaries (the perifascicular atrophy seen on muscle biopsy reflects this ischaemic pattern). The same complement-mediated process affects the skin, producing the heliotrope rash and Gottron papules. Anti-TIF1-gamma and anti-NXP-2 are antibodies against intracellular transcriptional regulators; their presence in the serum marks the subgroup of patients whose immune response is most strongly associated with an underlying tumour. The clinical implication is that removing the antigen source (the tumour) often dampens the immune response and improves the myositis — which is why the malignancy search and treatment are central, not peripheral, to the management." ^[1]

Q: A different patient presents with intensely pruritic grouped vesicles on the elbows and knees and a positive anti-tissue transglutaminase IgA. What is the diagnosis and management? ^[1]

A: "This is dermatitis herpetiformis, the specific cutaneous manifestation of coeliac disease. The diagnosis is confirmed by direct immunofluorescence of perilesional normal-appearing skin, showing granular IgA deposition in the dermal papillae — the biopsy must be of normal skin adjacent to the lesion, not the lesion itself, because the lesional skin shows non-specific inflammation. Almost all patients have gluten-sensitive enteropathy on duodenal biopsy even without gastrointestinal symptoms ^[4].

The management combines two strands. A strict lifelong gluten-free diet is definitive therapy — it resolves both the skin and the underlying enteropathy over months to years, reduces the risk of enteropathy-associated T-cell lymphoma and osteoporosis, and is the only treatment that addresses the underlying disease. Dapsone (50 to 200 mg orally daily) provides rapid symptomatic relief of the pruritus within days while the diet takes effect — dapsone inhibits neutrophil recruitment in the skin but does not treat the coeliac disease. Glucose-6-phosphate dehydrogenase deficiency must be excluded before starting dapsone (haemolysis risk), and full blood count and methaemoglobin monitoring are mandatory. I would arrange dietitian input, Coeliac Society referral, annual review of adherence and serology, iron studies, folate and B12, bone density, and a low threshold for investigation of any change in bowel symptoms given the lymphoma risk in untreated coeliac disease." ^[1]

Communication and shared decision-making

"I would sit with Mrs R and her husband in a quiet room, with the rheumatology nurse specialist and the gynaecological oncologist. I would explain that her rash and muscle weakness are part of a condition called dermatomyositis, which is an autoimmune inflammation of the skin and muscle. I would explain that this condition is sometimes linked to an underlying cancer, that the CT scan has found an ovarian mass that is likely to be the trigger, and that treating the ovarian cancer often improves the muscle and skin disease. I would be honest that the next few weeks and months will be demanding — immunosuppressive medications with their side effects, the gynaecological oncology evaluation and likely surgery, the monitoring of her swallow and breathing, and the uncertainty about the stage of the ovarian cancer. I would reassure her that the team will coordinate care, that the dermatomyositis often responds well to the immunosuppression and to treatment of the cancer, and that supportive care (physiotherapy, dietetics, psychology, cancer support) is part of the plan. I would document the shared decisions, arrange follow-up with clear safety-netting for any new symptoms (fever, worsening swallow or breathing, rash change), and offer to bring in her adult children and her general practitioner for a family meeting." ^[1]