Skin manifestations of systemic disease — branching viva

Opening question

Examiner: Take me through this child. What is the skin sign, and what is your frame for the work-up? [1]

Candidate: The tender, warm, bilateral red nodules over the shins are erythema nodosum, a reactive septal panniculitis. My frame is the recognise, investigate and refer approach: the skin sign is a door to an underlying systemic disease, so I will not treat it as a primary skin disease. I will chase the trigger — in his age group a recent streptococcal sore throat is the commonest cause — and the nodules will resolve over weeks as the trigger settles. [1]

Examiner: How do you classify cutaneous manifestations of systemic disease more broadly? [1]

Candidate: By mechanism, into six families. The reactive erythemas (erythema nodosum, erythema multiforme, Gianotti-Crosti) signal infection and hypersensitivity. The neutrophilic dermatoses (Sweet syndrome, pyoderma gangrenosum) point to inflammatory bowel disease and malignancy. The metabolic and endocrine markers (acanthosis nigricans, necrobiosis lipoidica, xanthomas) flag insulin resistance and diabetes. The gastrointestinal and nutritional dermatoses (dermatitis herpetiformis, acrodermatitis enteropathica) name the gut and the diet. The haematological and neoplastic markers (petechiae, blueberry muffin baby) warn of leukaemia and septicaemia. And the neurocutaneous syndromes (neurofibromatosis type 1, tuberous sclerosis, Sturge-Weber) carry their own diagnostic criteria. [1] [8]

Branch 1 — the reactive erythema

Examiner: What is the mechanism of erythema nodosum, and what causes it in children? [1]

Candidate: It is a type IV hypersensitivity reaction in the subcutaneous fat — immune complexes and T-cell activity produce a septal panniculitis with neutrophil and giant-cell infiltration of the fibrous septa. In children, group A streptococcal pharyngitis is the commonest identified cause, and the sore throat two weeks earlier fits. The differential also includes tuberculosis and sarcoidosis, inflammatory bowel disease in the older child, and drugs such as the oral contraceptive pill and sulfonamides. [1]

Examiner: How would you confirm the streptococcal cause? [1]

Candidate: With a throat swab and a rising antistreptolysin-O titre, alongside a chest radiograph and a tuberculin skin test or interferon-gamma release assay to exclude tuberculosis, and inflammatory markers. The streptococcal cause is confirmed by the serology, and treating it settles the nodules. The nodules themselves need no biopsy — the clinical picture is characteristic, and they resolve over three to six weeks without ulcerating or scarring. [1]

Branch 2 — the gastrointestinal door

Examiner: Suppose a child has intensely itchy grouped blisters on the elbows and buttocks. What is that, and what does it signal? [6]

Candidate: That is dermatitis herpetiformis, the cutaneous face of coeliac disease. The intensely pruritic, grouped vesicles on the elbows, knees and buttocks are driven by IgA autoantibodies against epidermal transglutaminase, and almost every affected child has gluten-sensitive enteropathy, even when the gut is silent. I confirm with coeliac serology — immunoglobulin A anti-tissue transglutaminase and anti-endomysial antibodies — and a duodenal biopsy while the child is on gluten, and a skin biopsy for immunofluorescence shows granular IgA in the dermal papillae. [5] [6]

Examiner: How do you treat it? [5]

Candidate: The definitive treatment is a strict, lifelong gluten-free diet, which clears the skin over months as the enteropathy heals. For rapid itch control while the diet takes effect, I add dapsone, screening for glucose-6-phosphate dehydrogenase deficiency first and monitoring for haemolysis and methaemoglobinaemia. The skin sign is a door — treating the itch alone with dapsone without the diet leaves the growth failure, the iron deficiency and the lymphoma risk of untreated coeliac disease unaddressed. [5] [6]

Branch 3 — the neurocutaneous syndromes

Examiner: A child is referred with multiple café-au-lait macules and axillary freckling. How do you approach that? [7]

Candidate: I apply the revised neurofibromatosis type 1 diagnostic criteria. The clinical criteria are two or more of: six or more café-au-lait macules of at least five millimetres in greatest diameter prepubertally or at least fifteen millimetres postpubertally; axillary or inguinal freckling; two or more neurofibromas or one plexiform; optic pathway glioma; two or more Lisch nodules; an osseous dysplasia; and a first-degree relative. I count and measure the macules, examine for freckling and neurofibromas, and refer to clinical genetics, because the criteria are clinical and a generalist can apply them at the bedside. [7]

Examiner: And a child with seizures and ash-leaf macules? [8]

Candidate: That is tuberous sclerosis complex. I apply the updated international criteria — the major criteria include hypomelanotic macules, facial angiofibromas, the shagreen patch and periungual fibromas, and a pathogenic TSC1 or TSC2 variant is now sufficient for the diagnosis. I arrange genetic testing and set up multidisciplinary surveillance for epilepsy, subependymal giant cell astrocytoma, renal angiomyolipoma and cardiac rhabdomyoma, because the skin signs are often present long before the seizures. [8]

Branch 4 — the emergencies

Examiner: What are the dangerous cutaneous signs of systemic disease in children? [9]

Candidate: Three in particular. A febrile child with rapidly evolving non-blanching purpura is meningococcal septicaemia or acute leukaemia — parenteral antibiotics within the first hour and intensive care. A neonate with widespread dark blue-red papules is the blueberry muffin baby of congenital infection or congenital leukaemia or neuroblastoma — urgent investigation. And an infant with a forehead or upper-eyelid port-wine stain may have Sturge-Weber syndrome, at risk of glaucoma, seizures and stroke-like episodes — urgent neuroimaging and ophthalmology. Each is the skin speaking for a disease that can kill or maim. [9]

Examiner: Why is the port-wine stain in that distribution an emergency? [9]

Candidate: Because the somatic GNAQ mutation that produces the capillary malformation in the V1 distribution may also produce the leptomeningeal angiomatosis of Sturge-Weber syndrome, with a risk of glaucoma from infancy and of seizures, stroke-like episodes and developmental impairment. The absence of seizures in early infancy does not exclude it. I arrange neuroimaging to define the leptomeningeal involvement and urgent ophthalmology for the glaucoma, and the port-wine stain itself is treated with pulsed-dye laser as part of the longer-term plan. [9]

Wrap

Examiner: Summarise the cutaneous manifestations of systemic disease stance in one sentence. [1]

Candidate: The skin is a window to systemic disease — group the signs by mechanism, apply the recognise, investigate the underlying disease, and refer framework, confirm the cause the sign dictates (a strep titre for erythema nodosum, coeliac serology for dermatitis herpetiformis, fasting glucose for acanthosis nigricans), treat the cause, and never miss the emergencies of meningococcal purpura, the blueberry muffin neonate and the V1 port-wine stain, because the skin that improves is the system that has healed. [1] [9]