Cutaneous Manifestations of Systemic Disease — Viva

Long Case Viva Defence

Candidate's opening statement (model answer)

"Mrs R is a 63-year-old woman presenting with a three-month history of progressive proximal muscle weakness, dysphagia to solids, and the pathognomonic cutaneous features of dermatomyositis — a heliotrope rash with periorbital violaceous erythema and oedema, Gottron papules over the metacarpophalangeal and proximal interphalangeal joints, periungual erythema with ragged cuticles and dilated nailfold capillary loops, and the photosensitive V and shawl signs over the chest and posterior shoulders. Her creatine kinase is 4800, aldolase is elevated, and her myositis antibody panel returns positive anti-TIF1-gamma with negative anti-Jo-1. There is no interstitial lung disease on high-resolution CT. Critically, a 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. The clinical picture is therefore anti-TIF1-gamma positive adult-onset dermatomyositis as a paraneoplastic phenomenon, with a presumed ovarian malignancy as the underlying cancer. 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) the respiratory and bulbar risks of the myositis; (4) the cutaneous disease itself, which is distressing and photosensitive; and (5) the psychosocial impact of a new diagnosis of both a muscle disease and a cancer. My priorities are to commence immediate immunosuppression for the myositis while simultaneously arranging urgent gynaecological oncology assessment of the ovarian mass, to assess and protect her swallow and respiratory function, to screen for aspiration and respiratory muscle involvement, and to coordinate a multidisciplinary plan." [1]

Examiner probing questions and model answers

Q1: "Walk me through your reasoning for why this patient needs a malignancy search, and what that search looks like." [1]

"Adult-onset dermatomyositis is a paraneoplastic disease. Roughly 15 to 25 per cent of adults with dermatomyositis have an underlying malignancy, and the risk clusters in the first three years around the diagnosis (Voulgaris et al, 2025) [4]. The myositis-specific antibodies refine the risk: anti-TIF1-gamma and anti-NXP-2 carry the strongest malignancy associations, while anti-Mi-2 carries a lower risk and anti-Jo-1 marks the antisynthetase syndrome with interstitial lung disease rather than cancer. This patient's anti-TIF1-gamma positivity places her in the highest-risk subgroup, so a structured malignancy search is non-negotiable.

The search is structured. For a woman of her age, it begins with a CT chest abdomen pelvis, which has already revealed an ovarian mass. I would add a pelvic ultrasound to characterise the mass, serum CA-125 (already elevated at 480), 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 the search must be thorough and guided by the antibody profile — anti-TIF1-gamma positivity is not a licence to stop at the first abnormality, but a mandate to be systematic. [1]

The temporal relationship supports the paraneoplastic interpretation. The dermatomyositis developed within months of the presumed ovarian cancer, the antibody is the one most strongly linked to cancer, and ovarian cancer is the classic association of paraneoplastic dermatomyositis in women. Treating the ovarian cancer often improves the dermatomyositis, which confirms the relationship." [1]

Q2: "How does anti-TIF1-gamma differ from anti-Jo-1 in clinical significance?" [1]

"Anti-TIF1-gamma and anti-Jo-1 are both myositis-specific antibodies, but they mark very different clinical phenotypes. Anti-TIF1-gamma is one of the two antibodies — with anti-NXP-2 — that carry the strongest malignancy associations in adult-onset dermatomyositis. Patients with anti-TIF1-gamma tend to have prominent cutaneous disease, a moderate myositis, and a low rate of interstitial lung disease, but a significantly elevated risk of an underlying solid tumour, particularly ovarian, lung, gastric, pancreatic and breast. This antibody tells me to prioritise the malignancy search. [1]

Anti-Jo-1, in contrast, is the prototypical antisynthetase antibody. It marks the antisynthetase syndrome, characterised by myositis, interstitial lung disease (often the dominant and most life-threatening feature), non-erosive arthritis, Raynaud phenomenon, mechanic's hands (thickened, fissured skin on the radial and palmar aspects of the fingers), and fever. The antisynthetase syndrome has a much lower malignancy association than anti-TIF1-gamma disease. The clinical implication is that a patient with anti-Jo-1 needs aggressive screening and management of interstitial lung disease — serial lung function and high-resolution CT, and often early immunosuppression including corticosteroids with a calcineurin inhibitor, mycophenolate, rituximab or antifibrotics — while a patient with anti-TIF1-gamma needs a structured malignancy search. This patient's antibody profile (anti-TIF1-gamma positive, anti-Jo-1 negative) tells me to prioritise the ovarian evaluation." [1]

Q3: "How would your management change if she developed respiratory muscle weakness with a falling FVC?" [1]

"Respiratory muscle involvement is a high-stakes complication of dermatomyositis. If her forced vital capacity falls below 60 per cent of predicted or shows a clear downward trend, she is at risk of type 2 respiratory failure from respiratory muscle fatigue. My approach would be: [1]

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

Second, support ventilation. Non-invasive ventilation (BiPAP) is the first step, to unload the fatiguing respiratory muscles and maintain gas exchange overnight. I would monitor blood gases, and if she progresses to hypercapnic respiratory failure despite non-invasive support, she may need intubation and mechanical ventilation — but the prognosis in that situation is guarded and would prompt a discussion of goals of care. [1]

Third, address the aspiration risk. The dysphagia reflects involvement of the pharyngeal and upper oesophageal striated muscle. I would involve speech pathology for a swallow assessment (modified barium swallow or fibreoptic endoscopic evaluation of swallow), thicken fluids and modify the diet, and consider nasogastric or PEG feeding if the swallow is unsafe. Aspiration pneumonia is a leading cause of death in severe dermatomyositis. [1]

Fourth, treat the underlying cancer. The paraneoplastic myositis often improves with treatment of the ovarian tumour, so the gynaecological oncology plan proceeds in parallel." [1]

Q4: "A patient with dermatitis herpetiformis asks why she needs a lifelong gluten-free diet when the rash responds so quickly to dapsone. How do you answer?" [1]

"This is an important question that gets to the heart of the disease. Dermatitis herpetiformis is the specific cutaneous manifestation of coeliac disease — the patient has gluten-sensitive enteropathy on duodenal biopsy even if she has no gastrointestinal symptoms [5]. The rash responds to dapsone within days because dapsone blocks neutrophil recruitment in the skin, but dapsone does NOT treat the underlying coeliac disease.

The lifelong gluten-free diet does three things that dapsone cannot. First, it resolves the underlying enteropathy — the villous atrophy in the duodenum heals over months to years, restoring normal absorption of iron, folate, B12 and calcium. Second, it resolves the skin disease at its source — over months, the granular IgA deposition in the dermal papillae fades and the rash stops recurring. Third, and most importantly, it reduces the long-term complications of untreated coeliac disease — the risk of enteropathy-associated T-cell lymphoma is significantly higher in patients who do not adhere to the diet, and the risks of osteoporosis, iron deficiency anaemia, other autoimmune disease and fertility problems are also reduced. [1]

So dapsone is a bridge, not a destination. I would explain that the diet is the definitive treatment for both the skin and the bowel, that strict adherence resolves both over time, that even small amounts of gluten provoke relapse, and that the dietitian and Coeliac Society provide essential support. I would continue dapsone at the lowest effective dose for the first months while the diet takes effect, and taper it as the rash comes under dietary control. I would also arrange annual review of adherence, iron, folate, B12, bone density and coeliac serology." [1]

Q5: "How would you distinguish calciphylaxis from pyoderma gangrenosum at the bedside, and why does the distinction matter?" [1]

"These two conditions both produce painful lower-leg lesions but their management is opposite, so the distinction is high-stakes. The discriminating features are: [1]

First, the clinical context. Calciphylaxis occurs in patients with advanced chronic kidney disease or dialysis, typically with hyperphosphataemia, a high calcium-phosphate product, and often on warfarin. Pyoderma gangrenosum occurs in patients with inflammatory bowel disease, arthritis, or haematological malignancy — and may also be idiopathic. [1]

Second, the morphology. Calciphylaxis produces exquisitely tender, indurated, purpuric plaques that progress to necrotic black eschars with surrounding livedo — the lesion is purpuric and necrotic from the start, reflecting vascular occlusion and infarction. Pyoderma gangrenosum produces painful ulcers with undermined, violaceous, boggy borders, often beginning as pustules at sites of minor trauma (pathergy). [1]

Third, the distribution. Calciphylaxis favours the proximal lower extremities (thighs) and lower abdomen, areas with more adipose tissue. Pyoderma gangrenosum favours the lower legs but can occur anywhere, including around stomas (peristomal pyoderma gangrenosum). [1]

Fourth, the biopsy. Calciphylaxis shows calcification of small and medium subcutaneous vessels with intimal hyperplasia and thrombosis. Pyoderma gangrenosum has no pathognomonic histology — it shows non-specific neutrophilic inflammation. [1]

The distinction matters because the management is opposite. Calciphylaxis requires surgical debridement of necrotic tissue to prevent infection and sepsis, intravenous sodium thiosulfate, correction of calcium-phosphate, and cessation of warfarin [2] [3]. Pyoderma gangrenosum is worsened by surgical debridement (pathergy), and is treated with systemic corticosteroids, ciclosporin, or biologics such as infliximab. Debriding pyoderma gangrenosum is the cardinal error; not debriding necrotic calciphylaxis is the cardinal error. Confusing the two can be fatal."

Q6: "What is the significance of the sign of Leser-Trelat, and how do you counsel a patient in whom you suspect it?" [1]

"The sign of Leser-Trelat is the sudden eruption of numerous seborrhoeic keratoses, often with pruritus, in association with an underlying internal malignancy — classically adenocarcinoma of the gastrointestinal tract (gastric, colonic, pancreatic) (Schwartz, 1996) [6]. The proposed mechanism is tumour-derived growth factors, particularly transforming growth factor-alpha and heparin-binding epidermal growth factor, driving epidermal proliferation. The sign often coexists with malignant acanthosis nigricans and tripe palms, particularly in gastric adenocarcinoma.

There is honest clinical debate around the sign, because both seborrhoeic keratoses and internal malignancy are common in older people, so a causal association is statistically difficult to prove. However, the consensus is that an abrupt change in number, distribution and symptom pattern of seborrhoeic keratoses — especially in a younger patient, or with pruritus, or with acanthosis nigricans and tripe palms — justifies a thorough clinical evaluation. [1]

In counselling a patient in whom I suspect the sign, I would be honest about the uncertainty while being clear about the plan. I would explain that seborrhoeic keratoses are common, but that the sudden appearance of many of them, together with the other features, makes me want to do a careful check for any internal problem. I would arrange age-appropriate cancer screening including a thorough history and examination, blood tests, and upper and lower gastrointestinal endoscopy and imaging guided by any symptoms. I would avoid causing undue alarm while being honest that the evaluation is necessary. The principle is that the paraneoplastic skin sign is a clue to investigate, not a diagnosis in itself." [1]

Short Case Discussion

Systematic skin examination

Examiner instruction: "Examine this patient's skin. She is a 58-year-old woman with a chronic multisystem illness." [1]

Candidate's model answer: [1]

"I would like to examine this patient's skin systematically — from head to toe, including the scalp, face, oral mucosa, hands and nails, trunk, flexures, and lower limbs, palpating lesions where indicated, and then screening for relevant systemic signs. [1]

Face: I am inspecting the face. There is a violaceous erythema with oedema of the upper eyelids — a heliotrope rash, which is the most specific cutaneous marker of dermatomyositis. There is also a malar distribution of violaceous erythema over the cheeks. I would specifically check whether the nasolabial folds are involved or spared. [1]

Hands and nails: On the dorsal hands there are violaceous papules over the metacarpophalangeal and proximal interphalangeal joints — Gottron papules, pathognomonic of dermatomyositis. There is periungual erythema, the cuticles are ragged (Samitz sign), and the nailfold capillaries are dilated with dropout on inspection. There is no sclerodactyly, no clubbing, and no Janeway lesions or Osler nodes. [1]

Trunk: On the upper trunk there is a photosensitive violaceous erythema in a V distribution over the anterior chest and a shawl distribution over the posterior shoulders and neck — the V and shawl signs of dermatomyositis. I do not see spider naevi or palmar erythema to suggest chronic liver disease, and I do not see the sudden eruption of multiple seborrhoeic keratoses that would raise the sign of Leser-Trelat. [1]

Lower limbs: On the lower limbs there are no palpable purpuric lesions to suggest vasculitis, no tender erythematous nodules on the shins to suggest erythema nodosum, no necrotic purpuric plaques to suggest calciphylaxis, and no ulcers with undermined violaceous borders to suggest pyoderma gangrenosum. [1]

Synthesis: My findings are a heliotrope rash, Gottron papules, periungual erythema with ragged cuticles and dilated nailfold capillaries, and the V and shawl signs. This combination is pathognomonic of dermatomyositis. I would like to complete my examination by measuring her muscle strength (looking for proximal weakness), assessing her swallow, checking her respiratory function, and screening for interstitial lung disease. I would measure a creatine kinase and a myositis antibody panel, and given that adult-onset dermatomyositis carries a paraneoplastic risk — particularly with anti-TIF1-gamma or anti-NXP-2 — I would undertake a structured malignancy search with CT chest abdomen pelvis, pelvic ultrasound, mammography, and upper and lower gastrointestinal endoscopy." [1]

Examiner: "What is the mechanism of the heliotrope rash, and how does it differ from the malar rash of SLE?" [1]

"The heliotrope rash of dermatomyositis is a violaceous erythema with oedema of the upper eyelids, caused by a complement-mediated microangiopathy of the dermis — the same pathological process that affects the muscle. The colour is described as heliotrope, a purplish hue resembling the heliotrope flower. It is the most specific cutaneous marker of dermatomyositis. [1]

The malar rash of systemic lupus erythematosus is a fixed erythematous, photosensitive rash over the cheeks and bridge of the nose that characteristically spares the nasolabial folds. The mechanism is immune complex deposition with complement activation in the basal layer of the epidermis and the dermal-epidermal junction. The key bedside distinctions are: the malar rash is on the cheeks and nose and spares the nasolabial folds, while the heliotrope rash is on the upper eyelids with oedema; the malar rash is flat and erythematous, while the heliotrope is violaceous with oedema; and the company they keep differs — the malar rash of SLE coexists with Gottron-negative, oral ulcerative, arthritic, cytopenic disease, while the heliotrope rash of dermatomyositis coexists with Gottron papules, proximal myositis, and malignancy risk. Discoid lupus, in contrast, produces scarring plaques with follicular plugging and a carpet-tack sign, and does not scar in the malar distribution." [1]

Examiner: "Name three other paraneoplastic skin signs and their classic underlying malignancies." [1]

"The high-yield paraneoplastic skin signs and their classic underlying malignancies are: malignant acanthosis nigricans with tripe palms (gastric adenocarcinoma); the sign of Leser-Trelat, the sudden eruption of seborrhoeic keratoses (GI adenocarcinoma, particularly gastric, colonic, pancreatic); Trousseau syndrome, migratory thrombophlebitis (pancreatic adenocarcinoma and other mucin-producing tumours) [7]; necrolytic migratory erythema (glucagonoma, a pancreatic alpha-cell neuroendocrine tumour) [1]; Sweet syndrome with cytopenias or blasts (acute myeloid leukaemia and myelodysplasia) [8]; erythema gyratum repens (lung and other solid tumours); and acquired ichthyosis (lymphoma, particularly Hodgkin disease). The unifying principle is that the skin sign often precedes the diagnosis of the underlying cancer, so recognising the cutaneous marker is the event that triggers the malignancy search."