Paeds · paediatric-dermatology
Skin manifestations of systemic disease
Also known as Cutaneous signs of systemic disease · Dermatologic markers of internal disease · Skin as a window to systemic disease · Neurocutaneous syndromes · Reactive erythemas · Paraneoplastic dermatoses
Fellowship topic on cutaneous manifestations of systemic disease in children: the skin as a window to internal disease. Covers the reactive erythemas and panniculitides (erythema nodosum signalling streptococcal infection, sarcoidosis and inflammatory bowel disease; erythema multiforme and mycoplasma-induced rash and mucositis after HSV and Mycoplasma; Gianotti-Crosti papular acrodermatitis as a viral exanthem), the neutrophilic dermatoses (Sweet syndrome and pyoderma gangrenosum linked to inflammatory bowel disease and malignancy), the metabolic and endocrine markers (acanthosis nigricans as insulin resistance and obesity and type 2 diabetes; necrobiosis lipoidica and xanthomas), the gastrointestinal and nutritional dermatoses (dermatitis herpetiformis as the cutaneous face of coeliac disease; acrodermatitis enteropathica as zinc deficiency), the haematological and neoplastic markers (petechiae and purpura in leukaemia and septicaemia, the blueberry muffin neonate), and the neurocutaneous phakomatoses (neurofibromatosis type 1 with its revised diagnostic criteria, tuberous sclerosis complex and the port-wine stain of Sturge-Weber syndrome). Built around recognise, investigate the underlying disease, and refer, grounded in the erythema nodosum and erythema multiforme and acanthosis nigricans reviews, the coeliac disease ESsCD guideline, the dermatitis herpetiformis update, the revised NF1 and updated TSC diagnostic criteria, the port-wine birthmark and Sweet syndrome reviews, the acrodermatitis enteropathica paper and the Gianotti-Crosti review.
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Target exams
Red flags
- A febrile, unwell child with rapidly evolving petechiae or purpura, especially non-blanching lesions on the limbs or trunk — think meningococcal septicaemia, disseminated intravascular coagulation or acute leukaemia; treat as a time-critical emergency
- A neonate with widespread dark blue-red, indurated papules and plaques — the blueberry muffin baby of congenital infection (cytomegalovirus, rubella, toxoplasmosis), haemolytic disease or congenital leukaemia or neuroblastoma; investigate urgently
- An infant with a facial port-wine stain in the forehead or upper eyelid (V1) distribution, seizures or developmental delay — Sturge-Weber syndrome; urgent neuroimaging and ophthalmology for glaucoma
- A child with hypopigmented ash-leaf macules presenting with infantile spasms or seizures — tuberous sclerosis complex; urgent developmental and neurological assessment
- An unwell child with painful erythematous plaques, fever and a high neutrophil count — Sweet syndrome may be the first sign of acute myeloid leukaemia or inflammatory bowel disease
Life stages
Care settings
Clinical exam formats
Board mappings
- General Paediatrics and Dermatology: recognition of reactive erythemas, acanthosis nigricans, dermatitis herpetiformis and petechiae as cutaneous markers of systemic disease; arrange targeted investigation and referral
- Genetics and Neurology: recognition of neurofibromatosis type 1, tuberous sclerosis complex and Sturge-Weber syndrome on skin examination
- Renewed curriculum — Dermatology and multisystem disease: pathophysiology linking cutaneous signs to metabolic, gastrointestinal, haematological and neoplastic disease
- Population child health: screening for insulin resistance in acanthosis nigricans and equitable access to specialist and genetic services
- General Paediatrics: diagnosis of cutaneous markers of systemic disease and the recognise, investigate the cause, and refer framework, including the emergencies of meningococcal purpura and the blueberry muffin neonate
- Neonatal and infant presentations: the blueberry muffin baby, port-wine stain and risk of Sturge-Weber syndrome
- Long Case / Structured discussion: a child with cutaneous signs that signal underlying systemic disease — recognition, differential, investigation pathway and multidisciplinary referral
- Communication station: explaining that a skin sign may reflect an internal disease and the rationale for blood tests and specialist referral
- Level 2 / 3 — Dermatology and multisystem presentations: cutaneous markers of systemic disease and the neurocutaneous syndromes
- Genetics: the phakomatoses and their diagnostic criteria
- Foundation of Practice (FOP): recognition of erythema nodosum, erythema multiforme, acanthosis nigricans, dermatitis herpetiformis and the neurocutaneous stigmata
- Applied Knowledge in Practice (AKP): investigation of a child in whom the skin sign suggests internal disease
- History-taking and management: the child with cutaneous markers of systemic disease, including the work-up and referral pathway
- Communication: explaining the link between a skin sign and an internal disease to a family
- General Pediatrics Content Outline — cutaneous manifestations of systemic disease: reactive erythemas, metabolic and nutritional markers, haematological signs and neurocutaneous syndromes
- Dermatology: recognition, differential and referral
- Genetics: neurofibromatosis type 1 and tuberous sclerosis complex diagnostic criteria
- Patient Care: recognition and timely investigation of cutaneous markers of systemic disease across reactive, metabolic, haematological and neurocutaneous categories
- Systems-Based Practice and Population Health: equitable access to specialist dermatology, genetics and metabolic services
- Medical Knowledge: the pathophysiology linking skin signs to internal disease, from immune complex deposition to somatic mosaicism
- Medical Expert: diagnosis and investigation of cutaneous manifestations of systemic disease and the neurocutaneous syndromes
- Health Advocate and Collaborator: coordinated multidisciplinary care for complex multisystem disease
- Communicator: explaining the systemic implications of a skin sign to children and families
Two cutaneous signals, two different diseases
Erythema nodosum
Acanthosis nigricans
Read a puzzling skin sign through six doors and the underlying disease is usually behind one of them. Reactive erythemas flag infection and hypersensitivity (erythema nodosum, erythema multiforme, Gianotti-Crosti). Neutrophilic dermatoses flag bowel and blood (Sweet syndrome, pyoderma gangrenosum). Metabolic and endocrine markers flag sugar and fat (acanthosis nigricans, necrobiosis lipoidica, xanthomas). Gastrointestinal and nutritional dermatoses flag the gut and the diet (dermatitis herpetiformis, acrodermatitis enteropathica). Haematological and neoplastic markers flag blood and cancer (petechiae, blueberry muffin baby). Neurocutaneous syndromes flag brain and gene (neurofibromatosis type 1, tuberous sclerosis, Sturge-Weber). [1] [8]
Overview & Definition
Picture a ten-year-old sent to the clinic with three weeks of tender red lumps on both shins. She is otherwise well, but the lesions hurt when she walks and her mother is frightened. The lumps are erythema nodosum — a reactive inflammation of the subcutaneous fat — and the first question is not what cream to prescribe but what the skin is reacting to: in her age group, a recent streptococcal sore throat is the commonest answer. The skin has spoken for a systemic event, and the clinician's job is to listen. [1]
Cutaneous manifestations of systemic disease are skin findings that arise from, or signal, a disorder beneath the skin. They span immune-complex reactions such as erythema nodosum, antibody-mediated blistering such as dermatitis herpetiformis, metabolic deposition such as acanthosis nigricans and xanthomas, nutrient depletion such as the zinc deficiency of acrodermatitis enteropathica, malignant infiltration such as leukaemia cutis and the blueberry muffin neonate, and the developmental mosaicism of the neurocutaneous syndromes. What unites them is that the visible lesion is a clue, and the correct response is to chase the internal disease it points to. [3] [8]
The clinician's task has three layers. The first is recognition — naming the skin sign and resisting the urge to treat it as a primary skin disease. The second is the targeted work-up — choosing the investigations that the lesion itself dictates, whether coeliac serology for dermatitis herpetiformis or a full blood count for the purpuric child. The third is the multidisciplinary referral — to dermatology, gastroenterology, endocrinology, haematology or clinical genetics, because these are conditions whose management belongs to a team, not to a single prescription pad. [5] [7]
References12ShowHide
- [1]Leung AKC; Leong KF; Lam JM Erythema nodosum. World J Pediatr, 2018.PMID 30269303
- [2]Canavan TN; Mathes EF; Frieden I; Shinkai K Mycoplasma pneumoniae-induced rash and mucositis as a syndrome distinct from Stevens-Johnson syndrome and erythema multiforme: a systematic review. J Am Acad Dermatol, 2015.PMID 25592340
- [3]Leung AKC; Lam JM; Barankin B; Leong KF; et al Acanthosis Nigricans: An Updated Review. Curr Pediatr Rev, 2022.PMID 36698243
- [4]Baselga Torres E; Torres-Pradilla M Cutaneous manifestations in children with diabetes mellitus and obesity. Actas Dermosifiliogr, 2014.PMID 24698434
- [5]Al-Toma A; Volta U; Auricchio R; Castillejo G; et al European Society for the Study of Coeliac Disease (ESsCD) guideline for coeliac disease and other gluten-related disorders. United European Gastroenterol J, 2019.PMID 31210940
- [6]Nguyen CN; Kim SJ Dermatitis Herpetiformis: An Update on Diagnosis, Disease Monitoring, and Management. Medicina (Kaunas), 2021.PMID 34441049
- [7]Legius E; Messiaen L; Wolkenstein P; Pancza P; et al Revised diagnostic criteria for neurofibromatosis type 1 and Legius syndrome: an international consensus recommendation. Genet Med, 2021.PMID 34012067
- [8]Northrup H; Aronow ME; Bebin EM; Bissler J; et al Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations. Pediatr Neurol, 2021.PMID 34399110
- [9]Poliner A; Fernandez Faith E; Blieden L; Kelly KM; et al Port-wine Birthmarks: Update on Diagnosis, Risk Assessment for Sturge-Weber Syndrome, and Management. Pediatr Rev, 2022.PMID 36045161
- [10]Villarreal-Villarreal CD; Ocampo-Candiani J; Villarreal-Martinez A Sweet Syndrome: A Review and Update. Actas Dermosifiliogr, 2016.PMID 26826881
- [11]Sivakumar A; Vageshappa RK; Kumari R Acrodermatitis Enteropathica. JAMA Dermatol, 2024.PMID 37938848
- [12]Leung AKC; Sergi CM; Lam JM; Leong KF Gianotti-Crosti syndrome (papular acrodermatitis of childhood) in the era of a viral recrudescence and vaccine opposition. World J Pediatr, 2019.PMID 31134587