Henoch-Schönlein Purpura, Kawasaki Disease vs MIS-C, Infantile Haemangiomas, and Common Pediatric Eruptions

Henoch-Schönlein Purpura, Kawasaki Disease vs MIS-C, and Pediatric Dermatology

Cutaneous manifestations in children frequently represent windows into systemic pathology. Distinguishing benign, self-limiting neonatal eruptions from immune-mediated vasculitides and severe hyperinflammatory syndromes is an essential paediatric competency. Henoch-Schönlein purpura, Kawasaki disease, and Multisystem Inflammatory Syndrome in Children (MIS-C) share overlapping inflammatory, vascular, and mucocutaneous findings, yet differ critically in their organ risks, hemodynamic stability, and targeted pharmacotherapeutics.

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Henoch-Schönlein Purpura (IgA Vasculitis)

Henoch-Schönlein Purpura (HSP)—formally classified as IgA Vasculitis (IgAV)—is the most common systemic vasculitis of childhood, accounting for over 50% of all paediatric vasculitis cases.

Pathophysiology and Epidemiology

• Immunopathogenesis: Triggered in genetically susceptible children by an upper respiratory tract infection (predominantly Group A Streptococcus, adenovirus, parvovirus B19) or gastrointestinal infection. The underlying mechanism involves aberrant O-glycosylation of polymeric IgA1 molecules. These undergalactosylated IgA1 molecules act as autoantigens, forming large circulating IgA1 immune complexes. These complexes deposit in small blood vessels (post-capillary venules, capillaries, and arterioles) within the skin, synovial membranes, gut wall, and renal glomeruli, activating the alternative complement pathway (C3 deposition) and triggering neutrophilic inflammation with endothelial necrosis (leukocytoclastic vasculitis).
• Epidemiology: Peak incidence occurs between 3 and 8 years of age (median 5–6 years), with a slight male predominance (1.5:1). HSP is uncommon in infants under 2 years.

                   [Mucosal Infection: GAS, Adenovirus, Parvovirus]
                                          |
                  Production of Aberrantly Glycosylated IgA1
                                          |
             Formation of Circulating IgA1-C3 Immune Complexes
                                          |
             Deposition in Small Blood Vessel Endothelium (Skin, Gut, Joint, Kidney)
                                          |
             [Leukocytoclastic Vasculitis: Fibrinoid Necrosis & Micro-thrombosis]
                                          |
     +--------------------+---------------+--------------------+--------------------+
     |                    |                                    |                    |
[Cutaneous]          [Articular]                       [Gastrointestinal]      [Renal Glomerular]
Palpable Purpura   Oligoarthritis / Arthralgias      Submucosal Edema / Ischemia  IgA Nephritis
- Lower extremities- Knees, Ankles                   - Colicky pain, Bleeding    - Hematuria, Proteinuria
- Buttocks         - Transient, Non-deforming        - ILEO-ILEAL INTUSSUSCEPTION- BP & Urine for 6-12 mo!
- Normal Platelets

The Classical Clinical Tetrad

1. Palpable Purpura (Mandatory Criterion): Symmetrical, raised, non-blanching macules and palpable purpuric papules and plaques. The lesions emerge in crops, often beginning as urticarial or erythematous macules that rapidly evolve into purpura.
   • Gravity-Dependent Distribution: Characteristically localized to the extensor surfaces of the lower extremities, buttocks, and perineum, sharply sparing the trunk and face in ambulatory children. In non-ambulatory infants, purpura can involve the face, ears, and upper extremities.
   • Hematological Hallmark: The purpura occurs with a normal or elevated platelet count and normal coagulation parameters, differentiating HSP from thrombocytopenic disorders (such as Immune Thrombocytopenia / ITP) and fulminant meningococcemia.
2. Arthralgia and Arthritis (65–85% of cases): Acute, painful periarticular swelling and tenderness predominantly affecting large, weight-bearing lower limb joints (knees and ankles). The arthritis is transient, oligoarticular, non-migratory, and non-deforming, resolving spontaneously within 1 to 2 weeks without causing permanent joint erosion or residual cartilage damage.
3. Gastrointestinal Manifestations (50–75% of cases): Severe, crampy, spasmodic periumbilical or generalized abdominal pain caused by submucosal bowel wall edema and intramural hemorrhage. Nausea, vomiting, and occult gastrointestinal blood loss or macroscopic melena/hematochezia are common.
   • Major Surgical Complication: Intussusception: Occurs in 2% to 4% of children with HSP. Unlike idiopathic intussusception (which is almost exclusively ileocolic), intussusception in HSP is ileo-ileal in 60% to 70% of cases, triggered by a focal intramural bowel wall hematoma acting as a lead point. Because an ileo-ileal intussusception does not reach the cecum or colon, pneumatic or hydrostatic enemas are ineffective and contraindicated; diagnosis requires urgent ultrasound, and treatment frequently demands operative manual reduction or segmental bowel resection.
4. Renal Involvement (HSP Nephritis, 30–50% of cases): Manifests as microscopic or macroscopic hematuria, sub-nephrotic or nephrotic-range proteinuria, arterial hypertension, and acute kidney injury. Glomerulonephritis is identical histologically to IgA Nephropathy (Berger disease), demonstrating mesangial IgA and C3 deposition on immunofluorescence.

Surveillance and Management Protocol

• Long-Term Prognostic Determinant: While articular, cutaneous, and gastrointestinal symptoms resolve within 4 to 8 weeks, renal involvement dictates lifelong morbidity and mortality. Up to 1% to 5% of paediatric HSP patients progress to end-stage renal disease (ESRD).
• Mandatory Monitoring Protocol: Serial assessment of blood pressure and first-morning urinalysis (checking for proteinuria and microscopic hematuria) is compulsory for all patients:
  • Weekly for the first 4 weeks.
  • Every 2 weeks through months 2 and 3.
  • Monthly until 6 to 12 months from diagnosis.
• Indications for Urgent Paediatric Nephrology Referral & Renal Biopsy:
  • Significant persistent proteinuria (spot urine protein:creatinine ratio >100 mg/mmol or 24-hour urine protein >1 g).
  • Frank nephrotic syndrome (heavy proteinuria, severe hypoalbuminemia, generalized edema).
  • Acute nephritic syndrome (hematuria, hypertension, elevated serum creatinine).
• Therapeutic Approach:
  • Supportive Care: Bed rest, oral hydration, and simple analgesia (paracetamol; judicious use of NSAIDs like ibuprofen only in the confirmed absence of active GI bleeding or significant renal impairment).
  • Systemic Corticosteroids (Oral Prednisolone 1–2 mg/kg/day for 1–2 weeks): Consider for severe abdominal pain or GI bleeding after clinical review and exclusion of intussusception; severe soft-tissue oedema also warrants specialist advice. Steroids can shorten abdominal symptoms, but an early short course does not prevent persistent IgAV nephritis. Established severe nephritis requires separate nephrology-directed treatment.
  • Severe Crescentic Nephritis: Managed with high-dose intravenous pulse methylprednisolone combined with cyclophosphamide, azathioprine, or mycophenolate mofetil.

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Kawasaki Disease versus MIS-C (PIMS-TS)

Kawasaki disease and Multisystem Inflammatory Syndrome in Children (MIS-C)—termed Paediatric Inflammatory Multisystem Syndrome Temporally associated with SARS-CoV-2 (PIMS-TS) in European guidelines—share mucocutaneous and vascular inflammation. However, distinct demographic, hemodynamic, cardiac, and laboratory divergences separate these two entities:

+---------------------------------------------------------------------------------------------------------+
|                                 KAWASAKI DISEASE vs MIS-C / PIMS-TS                                     |
+----------------------------------------------------+----------------------------------------------------+
| KAWASAKI DISEASE (Classical KD)                    | MIS-C / PIMS-TS                                    |
+----------------------------------------------------+----------------------------------------------------+
| • Infants & Toddlers (<5 years; peak 18-24 mo)     | • Older School-age & Adolescents (median 8-11 yr)   |
| • Unknown environmental/infectious trigger         | • Temporally linked to SARS-CoV-2 (2-6 wks post)   |
| • Coronary Artery Aneurysms (primary cardiac risk) | • Cardiogenic Shock & Left Ventricular Failure (EF) |
| • Normal or mildly elevated Troponin / BNP         | • MARKEDLY ELEVATED Troponin & NT-proBNP (>10,000) |
| • Prominent Thrombocytosis in 2nd-3rd week         | • Profound Lymphopenia, Thrombocytopenia, Coag     |
| • Normal or mild Ferritin elevation                | • EXTREME HYPERFERRITINEMIA & D-dimers (>2,000)    |
| • IVIG 2 g/kg + High-Dose Aspirin                  | • IVIG + Steroids; Inotropes if shock; assess thrombosis risk  |
+----------------------------------------------------+----------------------------------------------------+

Clinical and Pathological Comparison Table

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Infantile Haemangiomas

Infantile haemangiomas are the most frequent benign soft-tissue vascular neoplasms of infancy, developing in 4% to 5% of all infants (with higher rates in premature, low-birth-weight, and female infants).

Biology and Immunohistochemical Hallmark

Unlike vascular malformations (e.g., port-wine stains, venous malformations), which are present at birth and grow commensurately with the child without cellular proliferation, infantile haemangiomas are true neoplasms characterized by endothelial cell hyperplasia. They characteristically show intense immunohistochemical staining for GLUT-1 (Glucose Transporter Protein 1), identical to placental microvascular endothelium. Vascular malformations are strictly GLUT-1 negative.

Natural History: The Three Phases

1. Proliferating Phase (0 to 6 months): Usually absent at birth or present as a faint, pale, blanched, or telangiectatic macule. Rapid volumetric proliferation begins within the first 2 to 4 weeks of life, with the highest growth velocity occurring between months 2 and 3, typically stabilizing by month 6 (superficial lesions appear bright crimson and lobulated ["strawberry haemangioma"], while deep lesions appear bluish, warm, and rubbery).
2. Plateau Phase (6 to 12 months): Growth decelerates, stabilizing to match normal infant growth.
3. Involution Phase (1 to 7+ years): Spontaneous slow involution occurs. The center softens, turns dull grayish-purple, and flattens. The classical clinical rule of thumb is resolution at approximately 10% per year: 50% resolved by age 5, 70% by age 7, and 90% by age 9. Approximately 50% of involuted lesions leave residual fibrofatty tissue, telangiectasias, or skin laxity.

[Birth: Faint Telangiectasia] --> [0-6 mo: Rapid Proliferation] --> [6-12 mo: Plateau] --> [1-9 yr: Slow Involution (10%/yr)]
                                  * Peak expansion at 2-3 mo                               * 50% by 5 yr; 70% by 7 yr; 90% by 9 yr

High-Risk Anatomical Locations Requiring Urgent Intervention

While most uncomplicated infantile haemangiomas require only reassurance and active observation, specific presentations require urgent specialist assessment for functional, vital or disfiguring risks. Start systemic therapy when indicated; multiple lesions alone require screening rather than automatic treatment:

1. Periorbital / Periocular Haemangiomas: Even small lesions can compress the cornea or obstruct the visual axis, inducing astigmatism, ptosis, and irreversible stimulus-deprivation amblyopia. Urgent ophthalmology referral is mandatory.
2. Airway / Subglottic Haemangiomas & The 'Beard Distribution': Any haemangioma involving the cutaneous 'beard area' (chin, lower lip, mandible, and anterior neck) carries up to a 60% risk of concurrent symptomatic subglottic haemangioma. Affected infants present between 4 and 10 weeks of age with progressive biphasic stridor, barking cough, and respiratory failure (often misdiagnosed as recurrent croup). Immediate direct laryngoscopy and bronchoscopy are indicated.
3. Multiple Cutaneous Haemangiomas (≥5 lesions): Strongly associated with visceral haemangiomatosis, predominantly hepatic haemangiomas. All infants with ≥5 cutaneous haemangiomas must undergo screening abdominal ultrasonography. Hepatic lesions can cause:
   • High-output congestive heart failure secondary to massive hepatic arteriovenous shunting.
   • Consumptive Hypothyroidism: Hepatic haemangiomas overproduce type 3 iodothyronine deiodinase, an enzyme that rapidly catabolizes thyroid hormones (converting T4 to reverse T3 and T3 to T2). Profound hypothyroidism ensues, requiring massive replacement doses of levothyroxine to prevent irreversible neurodevelopmental cretinism.
4. Ulcerated Haemangiomas: Most common in the diaper/perineal area, lips, and neck folds; cause excruciating pain, secondary bacterial infection, bleeding, and severe permanent scarring.
5. Large Segmental Facial Haemangiomas (>5 cm): Carries high risk of PHACE Syndrome:
   • P: Posterior fossa malformations (Dandy-Walker malformation, cerebellar hypoplasia).
   • H: Hemangioma (large, plaque-like segmental facial distribution).
   • A: Arterial cerebrovascular anomalies (internal carotid dysgenesis, aneurysms).
   • C: Cardiac defects (coarctation of the aorta, aortic arch anomalies).
   • E: Eye abnormalities (microphthalmia, optic nerve hypoplasia).

Pharmacological Management: Oral Propranolol

• First-Line Standard of Care: Oral Propranolol (non-selective beta-adrenergic blocker) has completely replaced systemic corticosteroids as first-line therapy.
• Mechanism of Action: Induces rapid vasoconstriction (visible lightening within 48–72 hours), downregulates pro-angiogenic factors (VEGF and bFGF), and triggers endothelial cell apoptosis.
• Dosing Regimen: Initiated at 1 mg/kg/day, titrated up to a maintenance target of 2 to 3 mg/kg/day divided in 2 daily doses. Therapy is maintained throughout the proliferative phase until 12 to 14 months of age, followed by a gradual taper to prevent rebound regrowth.
• Pre-treatment Screening: Cardiovascular examination (heart rate, blood pressure, auscultation for murmurs); baseline ECG if bradycardia or familial heart block is suspected.

• Topical Alternative: For small, superficial, thin haemangiomas outside high-risk zones, topical Timolol maleate 0.5% gel-forming solution (1–2 drops applied twice daily) can be effective; systemic absorption and beta-blocker effects remain possible, especially in young/preterm infants or through ulcerated skin.

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Contact Dermatitis

Contact dermatitis is an eczematous reaction to an exposure, producing itchy, dry, cracked or blistering skin. Irritant dermatitis follows direct barrier injury, for example repeated soap, detergent or wet exposure. Allergic contact dermatitis follows an immune reaction to an allergen such as nickel or a cosmetic ingredient, often with delayed symptoms. Ask about new products and the distribution/timing of exposure; remove the trigger, restore the barrier with emollients and use an appropriate topical corticosteroid for inflammation. Persistent or recurrent suspected allergy may require dermatology assessment and patch testing to identify the allergen.

Sources: NHS contact dermatitis; diagnosis and patch testing.

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Common Neonatal and Pediatric Cutaneous Eruptions

Accurate clinical differentiation of common benign neonatal rashes prevents unnecessary laboratory investigations, maternal anxiety, and inappropriate antibiotic use:

                               [Common Paediatric Eruptions]
                                             |
       +--------------------+----------------+--------------------+--------------------+
       |                    |                                     |                    |
[Erythema Toxicum]      [Milia & Acne]                    [Seborrhoeic Derm]      [Infectious: Impetigo]
- Day 2-3 of life       - Milia: keratin cysts, nose      - Greasy yellow scale   - Honey-colored crusts
- Flea-bitten macules   - Cephalic pustulosis: 2-3 wk       (cradle cap)          - S. aureus / GAS
- PUSTULE = EOSINOPHILS   Malassezia colonisation         - NON-PRURITIC!         - Topical Mupirocin vs
- Benign, self-limiting - Spontaneous resolution         - Emollient / Ketoconazole Oral Flucloxacillin

1. Erythema Toxicum Neonatorum (ETN)

• Epidemiology & Timing: Occurs in up to 50% to 70% of healthy, full-term neonates, characteristically appearing on day 2 or 3 of life (rarely present at birth; onset after 2 weeks is exceptional).
• Lesion Morphology: Blotchy, irregular, erythematous macules (2–3 cm in diameter) with central 1–2 mm firm, pale white or yellow papules or pustules, imparting a distinct 'flea-bitten' appearance. Distributed across the chest, back, face, and proximal extremities, strictly sparing the palms and soles.
• Diagnostic Smear: A Wright- or Giemsa-stained smear of the pustular contents demonstrates a predominance of eosinophils (>90%) with no bacteria or fungal elements.
• Management: Entirely benign, asymptomatic, and self-limiting; spontaneous resolution occurs within 7 to 14 days without hyperpigmentation or scarring. Reassurance is the only intervention.

2. Milia

• Features: Present in up to 40% of neonates. Pinpoint (1–2 mm), pearly-white or yellowish, discrete, smooth, dome-shaped papules localized over the nose, cheeks, chin, and forehead.
• Pathology: Benign epidermal inclusion cysts containing laminated keratinaceous material trapped within hair follicles and sebaceous glands. When present on the palate, they are termed Epstein pearls (midline raphe) or Bohn nodules (alveolar ridges).
• Course: Spontaneously exfoliate and resolve within the first 2 to 4 weeks of life. No treatment.

3. Neonatal Cephalic Pustulosis (Neonatal Acne)

• Timing: Emerges at 2 to 3 weeks of age (distinguishing it from ETN, which peaks on days 2–3).
• Morphology: Multiple small, pinpoint inflammatory erythematous papules and pustules scattered over the cheeks, chin, forehead, and upper eyelids, with a complete absence of true comedones (blackheads/whiteheads).
• Pathogenesis: Inflammatory pustular reaction to colonization by Malassezia species (M. sympodialis, M. globosa) yeasts, amplified by maternal transplacental androgens.
• Management: Self-limiting over weeks to months; wash with mild soap and water. Topical 2% ketoconazole cream can be applied twice daily for severe or persistent inflammatory eruptions.

4. Seborrhoeic Dermatitis (Cradle Cap)

• Timing: Arises in infants aged 3 weeks to 3 months.
• Morphology: Thick, greasy, yellowish, adherent waxy crusts and scales overlying an erythematous base on the scalp vertex ('cradle cap'), eyebrows, retroauricular folds, and diaper area.
• Crucial Diagnostic Differentiator: Unlike atopic dermatitis (infantile eczema), infant seborrhoeic dermatitis is completely non-pruritic. The infant sleeps peacefully, feeds normally, and is unbothered by the eruption.
• Management: Application of an emollient to soften scales, followed by gentle brushing with a soft baby brush and washing with a mild baby shampoo. For stubborn flexural lesions, a weak topical corticosteroid (1% hydrocortisone) or topical 2% ketoconazole cream for 5 to 7 days is curative.

5. Impetigo

• Microbiology: Superficial epidermal bacterial infection driven by Staphylococcus aureus (predominant) and Streptococcus pyogenes (Group A beta-hemolytic Streptococcus).
• Non-Bullous Impetigo (70% of cases): Fragile vesicular lesions that rapidly rupture, leaving moist red erosions that dry into pathognomonic, thick, golden 'honey-colored' adherent crusts on the face (perioral, perinasal) and extremities.
• Bullous Impetigo (30% of cases): Caused by S. aureus strains producing exfoliative (epidermolytic) toxin A, which selectively cleaves desmoglein-1 in the superficial stratum granulosum. Manifests as large, flaccid, clear-to-turbid bullae that rupture easily, leaving a red glistening surface with a peripheral collarette of scale.
• Therapeutic Regimen:
  • Localized Lesions: Topical mupirocin 2% or fusidic acid 2% ointment applied three times daily for 5 to 7 days.
  • Widespread, Multiple, or Bullous Lesions: Oral beta-lactamase-resistant antibiotic: oral Flucloxacillin (first-line in Europe) or oral Co-amoxiclav / Cefalexin for 7 days; oral Clarithromycin in penicillin-allergic patients.

6. Molluscum Contagiosum

• Microbiology & Clinical Features: Benign cutaneous infection caused by the Molluscum Contagiosum Virus (MCV), a double-stranded DNA poxvirus. Spread via skin-to-skin contact, autoinoculation, or contaminated towels/pools. Presents as discrete, firm, smooth, dome-shaped, pearly, flesh-colored papules (2–5 mm) with central umbilication containing a white, curdy core of viral keratinocytes (molluscum bodies).
• Management: Spontaneous resolution occurs as cell-mediated immunity matures over 6 to 18 months. Destructive therapies (cryotherapy, curettage) cause pain and scarring and are strictly avoided in young children. Active inflammation with redness around lesions heralds impending immune clearance (the 'beginning of the end' sign).

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Hair Disorders

• Tinea capitis: scaly patches with broken hairs or black dots, sometimes with occipital lymphadenopathy or a kerion (a boggy, inflamed, pustular mass that is not a bacterial abscess and must not be incised). Confirm with microscopy and culture of scalp scrapings or plucked hairs. Treatment always requires an oral antifungal, because topical agents do not penetrate the hair follicle: terbinafine is preferred for Trichophyton species and griseofulvin for Microsporum species. An antifungal shampoo for the child and household reduces spread.
• Alopecia areata: autoimmune, non-scarring, well-defined smooth patches with "exclamation-mark" hairs at the margin, sometimes with nail pitting. It is associated with atopy, autoimmune thyroid disease and Down syndrome. Many patches regrow; options include topical or intralesional corticosteroids and specialist treatment for extensive disease.
• Telogen effluvium: diffuse shedding about 2–3 months after a stressor such as a febrile illness, surgery or rapid weight loss; it resolves spontaneously.
• Trichotillomania produces irregular patches with broken hairs of different lengths, and traction alopecia follows tight hairstyles.
• Hypertrichosis is excess hair in a non-androgen-dependent pattern (congenital or caused by drugs such as ciclosporin, minoxidil or phenytoin). Hirsutism is male-pattern terminal hair in girls from androgen excess, for example polycystic ovary syndrome, non-classic congenital adrenal hyperplasia or an androgen-secreting tumour; look for virilisation and accelerated growth. A lumbosacral hair tuft can mark occult spinal dysraphism.

Sources: ESPD guidelines for tinea capitis in children; British Association of Dermatologists tinea capitis guideline 2014.