Cutaneous small vessel vasculitis

Meet the patient

A 7-year-old boy, three days out from a sore throat, is brought in with raised purple spots over his ankles and shins that do not fade under a glass slide, sore knees that will not let him run, and two days of colicky peri-umbilical pain. The spots are palpable purpura — the hallmark. This is the IgA vasculitis (Henoch-Schönlein) tetrad: purpura, arthralgia, abdominal pain, and renal involvement.^[8]

Before you reach for a steroid, the single most important next test is a urinalysis with microscopy, plus a blood pressure. Renal involvement in IgA vasculitis is silent until it is late, and it is the kidney — not the rash — that decides this child's prognosis for the next twelve months.^[9]

The two questions that frame every case of palpable purpura are the two you will meet at 3am: is this an inflammatory vasculitis? (palpability answers at the bedside) and is there systemic — especially renal — involvement? (the urinalysis answers in thirty seconds). Hold those two and the rest of the page slots into place.^[1]

The one sign — palpable purpura, and why it is the discriminator

Palpable purpura on the lower legs is the hallmark of LCV — the single most useful clinical sign in vasculitis. Palpability is what separates an inflammatory purpura (vessel leaking, neutrophils in the wall) from a non-inflammatory one (thrombocytopenia, senile, scurvy, trauma — flat, not raised). Press every purpuric spot; if you can feel it, it is vasculitis until proven otherwise.^[1]

^[1]

Etymology — viva gold in two lines. Purpura is straight Latin — purpura, "purple", from the Greek porphyra, the murex shellfish that yielded the royal dye. Leukocytoclasia unpacks as leukos (white) plus kytos (cell) plus klasis (shattering): the "nuclear dust" on H&E is literally shattered white cells — neutrophil nuclei blown apart inside the vessel wall.^[6]

What CSVV is — and the four buckets of trigger (DRIM)

CSVV is immune-complex (Type III hypersensitivity) inflammation of the post-capillary venules in the superficial dermis. Roughly half of cases are primary (idiopathic); the other half are secondary — and the secondary half is where the marks, and the treatable causes, live.^[3]

The four buckets of trigger, remembered as DRIM:^[1]

^{[1] [5]}

Drugs and infections each account for about a fifth of secondary LCV; autoimmune disease and malignancy make up most of the rest. In adults, drugs are the commonest single trigger; in children, the trigger is usually a streptococcal upper-respiratory infection preceding IgA vasculitis. COVID-19 now sits firmly on the infection list — the 2025 Olson systematic review catalogues both post-viral and post-vaccine patterns.^[2][4]

The mechanism — immune complex to nuclear dust

The mechanism is Type III hypersensitivity: circulating immune complexes deposit in post-capillary venules, complement fires, neutrophils arrive, and the vessel wall is destroyed. The reason lesions favour the lower legs is hydrostatic — dependent venules are where complexes settle and where pressure drives them into the wall.^[1][5]

The six-step chain, every link examinable:^[6]

1. Immune complexes (drug, microbial antigen, or autoantibody) deposit in post-capillary venule walls — worst in dependent areas.
2. Complement activates — classical and alternative pathways; C3, C5a, and the C5b-9 membrane attack complex.
3. C5a recruits neutrophils, which release proteases, reactive oxygen species, and matrix metalloproteinases.
4. The vessel wall undergoes fibrinoid necrosis — eosinophilic, amorphous material replacing the wall.
5. Neutrophils die and fragment — leukocytoclasia, the nuclear dust.
6. The destroyed wall leaks — red blood cell extravasation into the dermis, clinically palpable purpura.^[1]

In IgA vasculitis the circulating complex is galactose-deficient IgA1; it deposits in dermal venules and in the glomerular mesangium, which is why the skin disease and the nephritis travel together — and why a rash on the legs is a reason to check the urine.^[9][10]

How common, and who

Cutaneous vasculitis runs at roughly 5-10 per million per year, and CSVV is the commonest pattern a dermatologist meets. IgA vasculitis is the commonest childhood vasculitis — about 10-20 per 100,000 children per year, peaking at age 3-10, slightly more often in boys, and classically in spring after an upper-respiratory infection.^[2]

^[2]

Clinical presentation — what you see at 3am

The rash arrives in crops over days, each crop lasting one to three weeks, new lesions appearing as old ones fade. The distribution is the giveaway: bilateral, symmetrical, on the lower legs and ankles, and on pressure points. Lesions coalesce into plaques, bullate over necrotic centres, or ulcerate.^[3]

The morphology variants carry diagnostic weight:^[2]

• Urticarial papules lasting over 24 hours point to urticarial vasculitis.
• Livedo reticularis points to vasculopathy, antiphospholipid syndrome.
• Nodules point to polyarteritis nodosa, erythema induratum.
• Retiform (angular, stellate) purpura points to levamisole-cut cocaine, cholesterol emboli, calciphylaxis.
• Digital necrosis points to severe systemic vasculitis (cryoglobulinaemic, ANCA-associated).^[6]

Never stop at the skin. In every patient, actively screen for systemic involvement — renal (haematuria, proteinuria, AKI), GI (abdominal pain, bleeding, perforation), joints (arthralgia), nerves (mononeuritis multiplex), and lungs (haemoptysis — think ANCA-associated).^[5]

Bedside assessment — the three questions

Examination answers three questions: is this really an inflammatory vasculitis, how extensive is the skin disease, and is there systemic involvement? Run the skin, the drug history, the joints, the abdomen, and the nerves — in that order.^[5][6]

• Palpability test — press every purpuric lesion. Palpable means inflammatory means vasculitis; non-palpable means thrombocytopenia, senile, or trauma. This single bedside move does more diagnostic work than any blood test.
• Diascopy (glass slide) — confirms non-blanching (extravasated RBCs) versus blanching (telangiectasia, vascular lesion).
• Distribution — dependent areas, pressure points, symmetry; in a bed-bound patient, check the sacrum and heels.^[2]
• Joints — arthralgia without effusion is classic for IgA vasculitis; frank synovitis points to RA or SLE overlap.
• Abdomen — tenderness in a child with IgA vasculitis raises intussusception (ileo-ileal); check for melena on the glove.
• Neurology — mononeuritis multiplex (foot drop, wrist drop) flags systemic ANCA-associated or cryoglobulinaemic vasculitis.
• ENT and chest — nasal crusting, saddle-nose, sinus disease (GPA); wheeze (EGPA); haemoptysis (diffuse alveolar haemorrhage).^[6]

The drug history is the most important bedside question in adult LCV. Review every new agent started in the one to three weeks before onset — prescribed, over-the-counter, herbal, supplement, and recreational. Name the high-yield culprits: penicillins, sulphonamides, NSAIDs, allopurinol, propylthiouracil, hydralazine, minocycline, and levamisole-cut cocaine.^[1][5]

The four named subtypes — DIF does the sorting

Direct immunofluorescence is the single most important discriminator among the LCV subtypes. The same H&E picture — fibrinoid necrosis, nuclear dust, RBC extravasation — hides four different diseases, and DIF prises them apart in one line: IgA, IgG/C3, or pauci-immune.^[6]

^[1]

The face-off that earns marks — DIF plus complement plus driver antigen together:^[6]

^[6]

The classic trap: a single H&E slide cannot tell these four apart — only DIF can. A pathology report that reads "leukocytoclastic vasculitis" without an IgA, IgG, or pauci-immune qualifier is an incomplete report. Always send DIF on a fresh, separate biopsy.^[6]

Deep dive: the four subtypes in detail — pathogenesis and treatment laddersShowHide

IgA vasculitis (HSP). Immune complexes containing galactose-deficient IgA1 deposit around the cutaneous vessels and drive mesangial proliferation in the glomerulus — which is why the skin disease and the nephritis travel together. The dominant clinical features: round, oval, or retiform palpable purpura predominantly on the lower legs, arthralgia or arthritis, gastrointestinal bleeding or pain, and glomerulonephritis with mesangial IgA deposits. IgA vasculitis resolves spontaneously in 94% of children and 89% of adults, so supportive treatment is the primary strategy for self-limited disease. Corticosteroids should not be used prophylactically — systematic reviews show they do not prevent complications. For severe gastrointestinal or renal manifestations, some studies report benefit from corticosteroids, combined with immunosuppressive drugs; randomised trials have demonstrated success with high-dose steroids, ciclosporin, and mycophenolate in treating glomerulonephritis. Short-term outcome tracks the severity of the gastrointestinal disease; long-term prognosis depends on the severity of the nephritis.^[8][9]

Cryoglobulinaemic vasculitis. Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 degrees Celsius — send the specimen warm to the lab. Type I cryoglobulinaemia consists of a single isotype of monoclonal immunoglobulin; types II and III are mixed cryoglobulinaemia containing both IgG and IgM. In most patients with mixed cryoglobulinaemia the aetiologic agent is hepatitis C; the mechanism is B-cell lymphoproliferation with autoantibody production. The systemic vasculitis ranges from purpura, arthralgia, and weakness to skin ulcers, neurological involvement, and renal disease. Treatment is modulated to the underlying disease and organ severity: antiviral therapy for hepatitis C, immunosuppression, and anti-CD20 B-cell depletion. For severe cryoglobulinaemic vasculitis — skin ulcers, active glomerulonephritis, or refractory peripheral neuropathy — a randomised trial showed rituximab (two 1 g infusions, repeated at relapse) was superior to conventional therapy (glucocorticoids, azathioprine or cyclophosphamide, or plasmapheresis) and could be maintained long term in most patients.^[14][13]

Urticarial vasculitis. Chronic or recurrent urticarial lesions in which individual wheals persist for 24 hours or longer and leave dusky hyperpigmentation behind are urticarial vasculitis — not urticaria. The disease is most often idiopathic but has been linked to drugs, infections, autoimmune connective tissue disease, myelodysplastic disorders, and malignancies, and can extend systemically — most often affecting the musculoskeletal system, kidneys, lungs, gastrointestinal tract, and eyes. In practice, antibiotics, dapsone, colchicine, and hydroxychloroquine are popular first-line therapies, especially for mild cutaneous disease. More severe cases may require immunosuppressives — methotrexate, mycophenolate mofetil, azathioprine, ciclosporin — plus corticosteroids; rituximab, omalizumab, and interleukin-1 inhibitors have shown promise for refractory cases.^[7]

ANCA-associated vasculitis with cutaneous involvement. Palpable purpura can be the presenting sign of ANCA-associated vasculitis — granulomatosis with polyangiitis (Wegener's) or microscopic polyangiitis — but systemic features dominate. For remission induction in severe ANCA-positive disease, rituximab 375 mg per square metre weekly for 4 weeks was noninferior to daily oral cyclophosphamide 2 mg/kg/day, both with glucocorticoids tapered off; rituximab was more efficacious in relapsing disease and as effective in patients with major renal disease or alveolar haemorrhage. In severe disease with an eGFR under 50 ml/min per 1.73 m2 or diffuse pulmonary haemorrhage, plasma exchange (seven exchanges within 14 days) did not reduce death or end-stage kidney disease overall. See the AAV topic for the full protocol.^[11][12]

^{[1] [11] [13] [12]}

Differential diagnosis — the mimics

The mimics fall into two families: non-inflammatory purpura (flat) and vasculopathy (livedoid, occlusive). The palpability test, the platelet count, and the history do most of the sorting before you reach the biopsy.^[1]

^[1]

Investigations — biopsy a FRESH lesion

Two biopsies from two fresh lesions: one for H&E, one for DIF — and both from lesions under 24-48 hours old. DIF needs a separate, newer lesion because immune deposits fade faster than the histology. Send the DIF specimen in Michel's medium, not formalin.^[5][6]

The classic trap: biopsying an old lesion. Once a purpuric lesion is over 48-72 hours old, the neutrophilic infiltrate has faded, the nuclear dust has been cleared, and the histology is non-diagnostic. Always biopsy a fresh lesion — under 24 hours if you can, under 48 hours at the outside — and send DIF from the newest lesion of all.^[6]

• H&E — leukocytoclastic vasculitis: fibrinoid necrosis of vessel walls, neutrophilic infiltrate, nuclear dust (leukocytoclasia), RBC extravasation.
• DIF — the key discriminator:
  • IgA deposition means IgA vasculitis (Henoch-Schönlein purpura).^[8][9]
  • IgG, IgM, and/or C3 means classical immune-complex LCV.
  • Pauci-immune (no deposition) means consider ANCA-associated vasculitis.^[6]

The systemic work-up — every patient, every time:^[5]

• Urinalysis — haematuria and proteinuria; the single most important screening test, because renal involvement is silent until late.
• Bloods — FBC, U&E, LFTs, CRP and ESR.
• Complement — C3 and C4; low points to cryoglobulinaemia, SLE, or urticarial vasculitis.
• Autoantibodies — ANA, ANCA, rheumatoid factor, anti-C1q (urticarial vasculitis).
• Infection screen — hepatitis B surface antigen, hepatitis C antibody, HIV.
• Cryoglobulins — if complement is low or hepatitis C is positive; keep the specimen warm to the lab.
• Serum protein electrophoresis — if paraproteinaemia is suspected.
• Chest X-ray — if pulmonary involvement or ANCA is positive.
• Age-appropriate malignancy screen — if no other trigger is found in an older patient.^[5]

Management — three steps

Remove the trigger, treat the skin, escalate for systemic disease — in that order. Skin-limited CSVV often resolves with trigger removal and leg elevation alone; systemic disease needs immunosuppression.^[5]

Step 1 — identify and remove the trigger

• Stop every potentially causative drug — especially anything started 1-3 weeks before onset, including OTC and supplements.^[5]
• Treat any identified infection — hepatitis C with DAAs, streptococcal pharyngitis, endocarditis.^[5]
• Manage the underlying disease — SLE, rheumatoid arthritis, malignancy.^[5]

Step 2 — skin-limited disease (mild to moderate)

• Rest and leg elevation — avoiding standing or walking reduces hydrostatic pressure and the formation of new lesions.^[5]
• Low-dose corticosteroids, colchicine, or other agents — the options when skin-limited disease needs more than rest.^[5]
• Dapsone, colchicine, and hydroxychloroquine — popular first-line therapies, especially for mild cutaneous disease.^[7]

Step 3 — systemic or severe disease

• Systemic disease — higher doses of corticosteroids or immunosuppressive agents, scaled to the severity of organ involvement and the underlying associated disease.^[5]
• Severe ANCA-associated vasculitis — induction with rituximab 375 mg per square metre weekly for 4 weeks (noninferior to daily oral cyclophosphamide 2 mg/kg/day; more efficacious in relapsing disease) plus glucocorticoids tapered off.^[11]
• Severe disease with renal failure or pulmonary haemorrhage — plasma exchange was tested in PEXIVAS and did not reduce death or end-stage kidney disease.^[12]
• Severe cryoglobulinaemic vasculitis — rituximab two 1 g infusions was superior to conventional therapy (glucocorticoids, azathioprine or cyclophosphamide, plasmapheresis).^[13]

Subtype-specific moves

• IgA vasculitis (HSP) — supportive care; analgesia; a short course of corticosteroids for severe GI or renal involvement; monitor urinalysis and BP for 6-12 months because delayed nephritis can appear months after the rash fades.^[8][9]
• Urticarial vasculitis — antihistamines (limited effect), hydroxychloroquine, dapsone, colchicine; systemic steroids or rituximab for the hypocomplementaemic/SLE-overlap form.^[7]
• Cryoglobulinaemic vasculitis — treat the underlying hepatitis C with direct-acting antivirals (cures the vasculitis in most); rituximab plus or minus plasmapheresis for refractory or severe disease.^[5]

Complications and pitfalls — where LCV does harm

The downstream consequences run from trivial post-inflammatory hyperpigmentation to life-threatening organ failure. The examiner expects you to anticipate each one — especially the kidney.^[1][5]

• Renal — the dominant determinant of prognosis. IgA vasculitis: nephritis in 30-50% of children, 1-2% progress to ESRD, 10-30% to chronic kidney disease. Cryoglobulinaemic: MPGN-pattern nephritis. ANCA-associated: rapidly progressive pauci-immune crescentic GN.^[9]
• Pulmonary haemorrhage — diffuse alveolar haemorrhage in pauci-immune LCV/AAV; high mortality without plasma exchange and induction immunosuppression.^[5]
• GI complications of IgA vasculitis — intussusception (ileo-ileal, unlike the ileo-colic pattern of idiopathic childhood intussusception; ultrasound shows the target sign), bowel-wall haematoma, perforation, massive bleeding. Steroids shorten abdominal pain and may reduce intussusception risk but do not prevent nephritis.^[8]
• Skin — ulceration, secondary infection, post-inflammatory hyperpigmentation (months to years); chronic relapsing course in roughly 10-20% of skin-limited disease.^[3]
• Peripheral neuropathy — mononeuritis multiplex in cryoglobulinaemic and ANCA-associated vasculitis; irreversible if treatment is delayed.^[5]

^{[5] [6] [8]}

Prognosis, special populations, and the evidence base

Skin-limited CSVV has an excellent prognosis — resolution in weeks to months, with a chronic relapsing course in about 10-20%. Systemic involvement (renal, GI, neuro) worsens it, and IgA vasculitis carries a long-term renal risk that demands follow-up.^[3][9]

• Children (IgA vasculitis/HSP) — the commonest childhood vasculitis; usually self-limiting over 4-6 weeks; renal follow-up for 6-12 months; corticosteroids only for severe GI or renal disease; prognosis generally excellent.^[8]
• Older adults — higher risk of underlying malignancy; drug-induced disease is more common; screen for myelodysplasia if LCV is persistent.^[5]
• Pregnancy — rare; manage with topical and mild systemic agents; avoid teratogenic immunosuppressants.^[5]

There is no single international guideline — management rests on expert consensus, the Chapel Hill Consensus Classification (which sorts vasculitis by vessel size and dominant immune-complex type), and the EULAR/PRES/PRINTO criteria for IgA vasculitis. Emerging territory: COVID-19-associated CSVV and rituximab for refractory IgA vasculitis.^[4][5][6]

Prevention is trigger control: document every identified drug trigger in the medical record (and warn the patient never to take it again), treat underlying infections (hepatitis C) and autoimmune disease, and use compression stockings to reduce recurrence in dependent purpura.^[1]

Ward-round test — stems you will be asked

Work these four without another resource. Each plants a trap the examiner loves. Answers behind the reveal.^[1]

Stem 1 — A 7-year-old boy with palpable purpura on the ankles, knee pain, and 48 hours of colicky abdominal pain. What is your single most important next investigation, and why?ShowHide

This is the IgA vasculitis (HSP) tetrad — nonthrombocytopenic palpable purpura plus arthritis plus abdominal pain, with renal involvement the complication that decides prognosis. Diagnostic testing is required only to exclude other causes of purpura, to identify renal involvement, and — if indicated — to determine its extent with biopsy: check a urinalysis at presentation. Imaging or endoscopy may be needed to assess organ complications. Supportive treatment is the primary strategy because IgA vasculitis resolves spontaneously in 94% of children; corticosteroids should not be used prophylactically — they do not prevent complications — but randomised trials show success with high-dose steroids, ciclosporin, and mycophenolate for treating glomerulonephritis and other complications. Six months of follow-up is prudent.

^[8]

Stem 2 — A 54-year-old woman with palpable purpura on the legs, arthralgia, and fatigue. Complement shows a low C4 with normal C3; hepatitis C antibody is positive. Diagnosis, mechanism, and first-line treatment?ShowHide

This is cryoglobulinaemic vasculitis — the triad of purpura, arthralgia, and weakness of mixed cryoglobulinaemia (types II/III contain both IgG and IgM; type I is monoclonal), with hepatitis C the aetiologic agent in most patients. Cryoglobulins precipitate below 37 degrees Celsius — send the specimen warm to the lab. Treatment is modulated to the underlying disease and organ severity: antiviral therapy for hepatitis C, immunosuppression, and anti-CD20 B-cell depletion. For severe disease — skin ulcers, active glomerulonephritis, refractory peripheral neuropathy — a randomised trial showed rituximab two 1 g infusions superior to conventional therapy (glucocorticoids, azathioprine or cyclophosphamide, plasmapheresis).

^{[14] [13]}

Stem 3 — A 35-year-old woman with wheals on the thighs and arms that last 36 hours, are painful rather than itchy, and leave brown marks when they fade. What distinguishes this from ordinary urticaria, and what is the discriminating blood test?ShowHide

This is urticarial vasculitis, not urticaria. The three discriminating bedside features: the lesions last over 24 hours (ordinary urticaria resolves within 24 hours), they are painful or burning rather than pruritic, and they leave residual purpura or post-inflammatory pigmentation when they resolve. Order complement (C3, C4, CH50) and anti-C1q antibodies. A hypocomplementaemic profile with anti-C1q positivity marks the hypocomplementaemic urticarial vasculitis (HUV) variant — SLE overlap, systemic features (arthritis, glomerulonephritis, serositis, obstructive lung disease), and a DIF showing C3 plus or minus IgG along the basement membrane and vessel wall. Treatment ladder: antihistamines, hydroxychloroquine, dapsone, colchicine; systemic steroids or rituximab for HUV/SLE-overlap disease.^[7]

^[7]

Stem 4 — A 68-year-old man with palpable purpura on the legs, haemoptysis, and a creatinine that has doubled in a week. DIF is pauci-immune. What is the diagnosis, and what do you do in the first hour?ShowHide

This is ANCA-associated vasculitis with a pulmonary-renal syndrome — palpable purpura plus diffuse alveolar haemorrhage plus rapidly progressive glomerulonephritis. In the first hour: secure the airway and oxygenation, send urgent ANCA and renal function, refer for renal biopsy, and begin remission induction. For induction in severe ANCA-associated vasculitis (granulomatosis with polyangiitis or microscopic polyangiitis), rituximab 375 mg per square metre weekly for 4 weeks was noninferior to daily oral cyclophosphamide 2 mg/kg/day, both with glucocorticoids tapered off — rituximab was more efficacious in relapsing disease and as effective in major renal disease or alveolar haemorrhage. Plasma exchange (seven exchanges within 14 days) did not reduce death or end-stage kidney disease overall.

^{[11] [12]}

Exam pearls and the mantra

^[1]

The mantra, one line, carry it to the exam hall: palpable purpura on the legs — biopsy it fresh, check the urine, find the trigger.^[1]

References15ShowHide

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2. [2]DeHoratius DM. Cutaneous small vessel vasculitis Postgrad Med, 2023.PMID 36524408
3. [3]Lotti T, Ghersetich I, Comacchi C, Jorizzo JL. Cutaneous small-vessel vasculitis J Am Acad Dermatol, 1998.PMID 9810883
4. [4]Olson KO, Patel S, Pathak P, et al. Cutaneous small vessel vasculitis in the COVID-19 era: a systematic review Skin Health Dis, 2025.PMID 40365256
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11. [11]Stone JH, Merkel PA, Spiera R, et al. Rituximab versus cyclophosphamide for ANCA-associated vasculitis N Engl J Med, 2010.PMID 20647199
12. [12]Walsh M, Merkel PA, Peh CA, et al. Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis N Engl J Med, 2020.PMID 32053298
13. [13]De Vita S, Quartuccio L, Isola M, et al. A randomized controlled trial of rituximab for the treatment of severe cryoglobulinemic vasculitis Arthritis Rheum, 2012.PMID 22147661
14. [14]Roccatello D, Saadoun D, Ramos-Casals M, et al. Cryoglobulinaemia Nat Rev Dis Primers, 2018.PMID 30072738
15. [15]Weiss PF, Feinstein JA, Luan X, et al. Effects of corticosteroid on Henoch-Schönlein purpura: a systematic review Pediatrics, 2007.PMID 17974746