What is the appropriate work‑up for a patient presenting with a purpuric rash?

Workup for Purpuric Rash

Begin with a focused history targeting medication exposure (especially within the past 2 months including over-the-counter drugs), tick bites, travel to endemic areas, and systemic symptoms such as fever, joint pain, abdominal pain, or mucosal involvement, as these clinical features rapidly narrow the differential diagnosis and guide immediate management decisions. 1

Immediate Clinical Assessment

Critical Red Flags Requiring Urgent Action

• Examine for skin pain, tenderness, or Nikolsky sign (epidermal detachment with lateral pressure), which indicates Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) requiring immediate drug cessation and transfer to specialized care 1, 2
• Assess all mucosal surfaces (eyes, mouth, nose, genitalia) for erosions or hemorrhagic mucositis, as mucosal involvement distinguishes SJS/TEN from other purpuric conditions 1
• Document body surface area (BSA) involvement using a body map, as >30% BSA with skin sloughing represents grade 4 toxicity requiring hospitalization and IV methylprednisolone 1-2 mg/kg 1, 2
• Check vital signs and assess for fever with systemic toxicity, which raises concern for meningococcemia, Rocky Mountain spotted fever, or purpura fulminans 1, 3, 4

Essential History Elements

• Record all medications taken in the previous 2 months with exact start dates, as drug-induced causes (particularly antibiotics, anticonvulsants, NSAIDs) are the most common etiology of serious purpuric eruptions 1
• Ask specifically about tick exposure during spring/summer months, as Rocky Mountain spotted fever presents with fever, headache, and purpuric rash that begins on extremities and spreads centrally, with case-fatality rates of 40-50% if treatment is delayed beyond day 8 1
• Obtain detailed travel history within the past year, particularly to malaria-endemic regions, as Plasmodium falciparum can cause purpuric rash with thrombocytopenia and progress to death within 24-48 hours 5
• Document timing of rash onset and progression pattern, noting whether lesions are spreading rapidly (suggesting vasculitis or SJS/TEN) versus stable 1, 2

Laboratory Workup

First-Line Essential Tests

• Complete blood count with differential and peripheral blood smear to distinguish isolated thrombocytopenia from pancytopenia and to identify schistocytes (suggesting thrombotic thrombocytopenic purpura), platelet clumping (pseudothrombocytopenia), or abnormal white cells 5, 6, 4
• Comprehensive metabolic panel including liver function tests, renal function, and electrolytes to assess for organ involvement and guide fluid management 1
• Coagulation studies (PT, PTT, fibrinogen) to exclude disseminated intravascular coagulation or coagulopathy 1, 4
• Erythrocyte sedimentation rate and C-reactive protein to assess for systemic inflammation suggesting vasculitis 1

Infection Screening

• HIV and hepatitis C serology in all adults regardless of risk factors, as both commonly cause thrombocytopenia with purpura and may precede other symptoms by years 5, 6
• Three sequential thick and thin blood films spaced 12 hours apart if any travel to malaria-endemic areas within the past year, as delayed malaria diagnosis is a preventable cause of death 5
• Mycoplasma serology when respiratory symptoms accompany purpura 1
• Blood cultures if fever is present to exclude bacterial sepsis or endocarditis 1, 3

Additional Testing Based on Clinical Context

• Urinalysis with microscopy to detect hematuria or proteinuria suggesting renal involvement in IgA vasculitis (Henoch-Schönlein purpura) or systemic vasculitis 7
• Chest X-ray to assess for pulmonary involvement in systemic disease 1
• Antinuclear antibodies, anti-dsDNA, and complement levels (C3/C4) when systemic lupus erythematosus is suspected based on young age, female sex, and multisystem involvement 5

Skin Biopsy Strategy

Obtain two biopsies: one from lesional skin adjacent to a blister for routine histopathology, and a second from perilesional skin sent unfixed for direct immunofluorescence to distinguish leukocytoclastic vasculitis from immunobullous disorders. 1

• Do not delay biopsy while waiting for laboratory results, as histopathology provides definitive diagnosis and guides treatment 2
• Biopsy fresh lesions less than 24-48 hours old for optimal diagnostic yield in suspected vasculitis 8
• Request direct immunofluorescence specifically to detect IgA deposition (IgA vasculitis) or other immune complex patterns 1, 7

Critical Management Pitfalls to Avoid

• Never start empiric corticosteroids before excluding infectious etiologies, as steroids can precipitate fulminant sepsis in undiagnosed malaria, disseminated tuberculosis, or bacterial infection 5
• Immediately discontinue all potential causative medications if SJS/TEN is in the differential diagnosis, as delay in drug cessation is the primary factor associated with mortality 1, 2
• Do not transfuse platelets for isolated thrombocytopenia without active bleeding, as this is not indicated in immune thrombocytopenic purpura or vasculitic processes and may worsen thrombotic microangiopathies 2
• Do not reassure patients with fever and purpura without completing urgent workup, as Rocky Mountain spotted fever, meningococcemia, and purpura fulminans can progress to death within hours 1, 3, 4

Special Populations

Patients with Splenomegaly and Thrombocytopenia

• Splenomegaly argues strongly against primary immune thrombocytopenic purpura (present in <3% of ITP patients), and mandates investigation for lymphoproliferative disorders, chronic liver disease, or myeloproliferative neoplasms 5
• Obtain abdominal CT or ultrasound to assess spleen size, liver architecture, and portal hypertension 5
• Bone marrow aspiration and biopsy with flow cytometry is mandatory if pancytopenia is present or if age >60 years with isolated thrombocytopenia to exclude myelodysplastic syndrome or leukemia 5

Pediatric Considerations

• IgA vasculitis (Henoch-Schönlein purpura) is the most common vasculitis in children, characterized by nonthrombocytopenic palpable purpura on lower extremities and buttocks, arthritis, and abdominal pain 7
• Spontaneous resolution occurs in 94% of children, making supportive care the primary management strategy 7
• Six months of follow-up with serial urinalysis is prudent to assess for renal involvement, which determines long-term prognosis 7