Cutaneous Manifestations of Systemic Disease — Written Clinical Reasoning

SAQ 1 — Integrated Management of Paraneoplastic Dermatomyositis (20 marks, 30 minutes)

Prompt: Outline your integrated management plan for this patient with anti-TIF1-gamma positive adult-onset dermatomyositis and a presumed ovarian malignancy, including: (a) the clinical reasoning that links the skin signs to the malignancy; (b) the immediate immunosuppressive strategy for the myositis and dysphagia; (c) the malignancy-specific evaluation and the role of the myositis antibody profile; (d) the respiratory and bulbar risk assessment; (e) the pharmacology of dapsone and why it is NOT appropriate here; and (f) the communication and shared decision-making with the patient and the multidisciplinary team. [1]

Model Answer

(a) Clinical reasoning linking the skin signs to the malignancy (3 marks): [1]

This patient has classic dermatomyositis — the pathognomonic heliotrope rash (violaceous periorbital erythema with oedema), Gottron papules (violaceous papules over the knuckles), the V and shawl signs (photosensitive rashes on the chest and posterior shoulders), ragged cuticles (Samitz sign) and dilated nailfold capillaries. The markedly elevated creatine kinase confirms the proximal myositis, and dysphagia reflects involvement of the pharyngeal and proximal oesophageal striated muscle. [1]

The critical reasoning is that adult-onset dermatomyositis is a paraneoplastic disease. Roughly 15 to 25 per cent of adults with dermatomyositis have an underlying malignancy, with the risk clustering in the first three years around the diagnosis [4]. The myositis-specific antibody profile refines this risk: anti-TIF1-gamma is one of the two antibodies (with anti-NXP-2) that carry the strongest malignancy associations. The CT finding of a complex adnexal mass with ascites and a markedly elevated CA-125 is consistent with ovarian malignancy — the classic and most frequently tested paraneoplastic association of dermatomyositis in women. The temporal clustering (the dermatomyositis presenting within months of the presumed ovarian cancer) is typical. The mechanism is a shared antigen between the tumour and regenerating muscle, triggering a complement-mediated microangiopathy of muscle and skin.

(b) Immediate immunosuppressive strategy for the myositis and dysphagia (4 marks): [1]

The myositis with a creatine kinase of 4800 and dysphagia is clinically significant — the dysphagia carries an aspiration risk and the muscle weakness a risk of respiratory muscle involvement. My immediate strategy is: [1]

• High-dose corticosteroids — oral prednisone 0.5 to 1 mg per kg per day (approximately 40 to 60 mg daily), with a proton pump inhibitor for gastric protection, bone protection (calcium, vitamin D, and a bisphosphonate if indicated), and pneumocystis prophylaxis with trimethoprim-sulfamethoxazole given the moderate-dose steroids and likely immunosuppressive.
• A steroid-sparing immunosuppressive — my preference is methotrexate (10 to 25 mg once weekly with folate) or azathioprine (1 to 2 mg per kg per day, checking thiopurine methyltransferase first) to allow earlier steroid taper. If the disease is aggressive or refractory, intravenous immunoglobulin (2 g per kg per month in divided doses) has evidence in dermatomyositis, particularly for the cutaneous disease and dysphagia.
• 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.
• Aspiration risk assessment — speech pathology review of swallow safety, consideration of modified barium swallow or fibreoptic endoscopic evaluation of swallow, and dietary modification (thickened fluids, soft diet) as required. [1]

(c) Malignancy-specific evaluation and the antibody profile (4 marks): [1]

The antibody profile is the key to risk stratification. Anti-TIF1-gamma positivity places this patient in the highest malignancy-risk subgroup. The CT finding of a complex adnexal mass with ascites and a CA-125 of 480 requires urgent gynaecological oncology referral for staging and surgical planning. The malignancy evaluation should include: [1]

• Gynaecological oncology referral for staging laparotomy or laparoscopy with total abdominal hysterectomy, bilateral salpingo-oophorectomy, omentectomy and debulking, depending on the staging and histology.
• Tumour markers — CA-125 (already elevated), CEA, and other markers as guided by the oncology team.
• Complete malignancy screen — because a patient can have more than one finding, I would also complete the age-appropriate screen with mammography and upper and lower gastrointestinal endoscopy if there are any other symptoms or if the ovarian findings do not fully explain the clinical picture. The principle is that anti-TIF1-gamma positive dermatomyositis demands a thorough and structured search.
• Principle of treatment — the dermatomyositis often improves with treatment of the underlying tumour (resection of the ovarian cancer). Immunosuppression is for symptom control and prevention of further muscle damage; it does not treat the cancer. [1]

(d) Respiratory and bulbar risk assessment (3 marks): [1]

Two high-stakes risks in dermatomyositis are respiratory muscle involvement and aspiration. My assessment: [1]

• Respiratory muscle function — serial forced vital capacity (FVC) at the bedside and in the lung function laboratory. An FVC below 60 per cent of predicted or a falling trend signals respiratory muscle weakness and the need for ventilatory support (non-invasive ventilation, BiPAP). I would also measure maximum inspiratory and expiratory pressures.
• Aspiration risk — the dysphagia reflects involvement of the striated muscle of the pharynx and upper oesophagus. Speech pathology assessment with a modified barium swallow or fibreoptic endoscopic evaluation of swallow (FEES) guides dietary modification and the need for nasogastric or PEG feeding if swallow is unsafe.
• Interstitial lung disease — although the high-resolution CT shows no ILD and anti-Jo-1 is negative (the antisynthetase antibody that most strongly marks ILD risk), I would still monitor with serial lung function and high-resolution CT during follow-up, as ILD can develop later. [1]

(e) Pharmacology of dapsone and why it is NOT appropriate here (3 marks): [1]

Dapsone (a sulfone anti-inflammatory that inhibits neutrophil myeloperoxidase and chemoattraction, dosed 50 to 200 mg orally daily) is the rapid symptomatic bridge therapy for dermatitis herpetiformis (the cutaneous manifestation of coeliac disease), where it controls the intensely pruritic vesicular eruption within days while the gluten-free diet takes months to work. Before starting dapsone, glucose-6-phosphate dehydrogenase (G6PD) deficiency must be excluded (haemolysis risk), and full blood count and methaemoglobin monitoring are mandatory for dose-related haemolysis, methaemoglobinaemia and agranulocytosis. [1]

Dapsone is NOT appropriate in this patient because her dermatosis is dermatomyositis, an antibody-mediated complement microangiopathy, not dermatitis herpetiformis (an IgA-mediated neutrophilic disorder). Dapsone has no role in the management of dermatomyositis. The appropriate immunosuppression is high-dose corticosteroids with a steroid-sparing agent, as outlined above. This distinction is a common exam trap — dapsone is specific to dermatitis herpetiformis and a small number of other neutrophilic dermatoses (Sweet syndrome, linear IgA bullous dermatosis), not to dermatomyositis or lupus. [1]

(f) Communication and shared decision-making (3 marks): [1]

I would sit with this patient, her family, and the multidisciplinary team (rheumatology, gynaecological oncology, dermatology, speech pathology, physiotherapy, dietetics, and a clinical nurse specialist). My communication would cover: [1]

• The diagnosis and the paraneoplastic relationship — explaining in plain language 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.
• The treatment plan in phases — the immediate immunosuppression for the myositis (with its risks and benefits), the swallow and respiratory assessment to keep her safe, the gynaecological oncology plan for the ovarian cancer, and the longer-term follow-up.
• Honesty about prognosis and the emotional burden — acknowledging that the diagnosis of both a muscle disease and a cancer is frightening, that the team will coordinate care and keep her informed, and that support (psychology, social work, cancer support services) is available.
• Shared decision-making — on the immunosuppressive regimen (risks and benefits), on the surgical approach to the ovarian cancer (informed by the staging and histology), and on advance care planning as appropriate. [1]

SAQ 2 — Calciphylaxis in a Dialysis Patient (10 marks)

Prompt: A 68-year-old woman with end-stage kidney disease from diabetic nephropathy on haemodialysis for four years presents with a one-week history of rapidly progressive, exquisitely tender, indurated purpuric plaques on the proximal thighs and lower abdomen that are progressing to necrotic black eschars with surrounding livedo. She has been on warfarin for atrial fibrillation. Calcium is 2.45 mmol per litre, phosphate 2.1 mmol per litre (high), parathyroid hormone 62 pmol per litre. Discuss your diagnosis, the pathophysiology, the immediate management, the prognosis, and the communication with the patient and family. [1]

Model Answer

(a) Diagnosis and pathophysiology (2 marks): [1]

The diagnosis is calciphylaxis (calcific uremic arteriolopathy) — the classic presentation in a dialysis patient of exquisitely tender, purpuric, indurated plaques progressing to necrosis in a proximal (thigh, abdomen) distribution. The pathophysiology is a vascular calcification syndrome: in the uraemic, hyperphosphataemic, inflamed milieu, vascular smooth muscle cells transform into osteoblast-like cells, depositing calcium in subcutaneous arterioles. This causes intimal proliferation, thrombosis and ischaemic infarction of the overlying skin and adipose tissue [2]. Risk factors in this patient include dialysis, hyperphosphataemia, high calcium-phosphate product, and warfarin (a significant and modifiable risk factor). The proximal distribution (thighs, lower abdomen) carries a worse prognosis than the distal pattern (lower legs).

(b) Immediate management (4 marks): [1]

Management is multidisciplinary and intensive — I would involve nephrology, dermatology, surgery, infectious diseases, the pain team and palliative care: [1]

• Surgical debridement of clearly necrotic tissue — to remove the necrotic eschar that is a culture medium for infection and a source of sepsis (the leading cause of death). This is the opposite of pyoderma gangrenosum, where surgical debridement is contraindicated due to pathergy.
• Intravenous sodium thiosulfate — 25 grams over one hour during the last hour of each haemodialysis session, three times weekly. It chelates calcium, acts as an antioxidant and vasodilator, and has observational evidence of improved pain and wound healing [3].
• Correction of calcium and phosphate — non-calcium-based phosphate binders (sevelamer, lanthanum), dialysate calcium adjustment, cinacalcet for the hyperparathyroidism, and dietary phosphate restriction with dietitian input.
• Cessation of warfarin — transition to low molecular weight heparin or a direct oral anticoagulant for her atrial fibrillation, acknowledging that warfarin is a significant, modifiable risk factor for calciphylaxis.
• Aggressive pain control — opioid analgesia as required, with the pain team and palliative care input, as calciphylaxis pain is typically severe.
• Early treatment of infection — wound swabs and blood cultures, broad-spectrum antibiotics at any sign of cellulitis or sepsis.

(c) Prognosis (2 marks): [1]

The prognosis is grave — one-year mortality exceeds 50 per cent, with sepsis from infected necrotic tissue the leading cause of death [2]. The proximal distribution in this patient carries the worse prognosis. Even with optimal management, wound healing is slow and many patients succumb to sepsis or complications of their comorbidities. Honest prognostic discussion with the patient and family from the outset is essential, with early palliative care involvement alongside the disease-directed therapy.

(d) Communication with the patient and family (2 marks): [1]

I would sit with the patient and her family in a quiet room with the nephrologist and a clinical nurse specialist. I would explain that she has a serious condition called calciphylaxis in which the small blood vessels in the skin become calcified and blocked, causing the skin to become painful and to break down; that this is a complication of her long-standing kidney disease and dialysis; that the goal of treatment is to support wound healing and prevent infection; that the treatment combines wound care, a medication called sodium thiosulfate given during dialysis, correction of her calcium and phosphate, and stopping the warfarin; that the pain will be actively managed; and that the outlook is serious with a high risk of complications. I would discuss goals of care and advance care planning, and the involvement of palliative care for symptom control and support. I would document the shared decisions and arrange follow-up. [1]