Differential Diagnosis: Pruritic Rash, Migratory Arthralgia, and Gastrointestinal Symptoms
The constellation of itchy rash, migrating joint pain/swelling, nausea, vomiting, and abdominal cramping most strongly suggests autoinflammatory syndromes (particularly TRAPS or MKD), serum sickness-like reactions, or parasitic infections, with the specific diagnosis dependent on fever pattern, rash characteristics, and exposure history.
Primary Diagnostic Considerations
Autoinflammatory Syndromes
Tumor Necrosis Factor Receptor-Associated Periodic Syndrome (TRAPS) presents with the exact symptom constellation described, featuring migratory rash, periorbital edema, abdominal pain, and myalgia during episodic attacks 1. The migratory nature of both the rash and joint involvement is particularly characteristic 1.
Mevalonate Kinase Deficiency (MKD) should be strongly considered, as it characteristically presents with:
- Periodic fever attacks lasting 4-6 days 1
- Urticarial or maculopapular rash 1
- Severe abdominal pain with vomiting and diarrhea 1
- Cervical lymphadenopathy and aphthous stomatitis 1
Cryopyrin-Associated Periodic Syndromes (CAPS) can present with urticaria-like rash, nausea, vomiting, and musculoskeletal symptoms, though joint involvement is typically less migratory than in TRAPS 1.
Parasitic Infections
Hookworm infection (Ancylostoma duodenale/Necator americanus) presents with transient pruritic maculopapular rash followed weeks later by nausea, vomiting, diarrhea, and abdominal pain 1. The migratory nature of symptoms reflects the parasite's tissue migration phase.
Trichinellosis should be considered if there is recent consumption of undercooked pork, presenting with upper abdominal pain, fever, vomiting, diarrhea, followed by severe myalgia, muscle weakness, periorbital edema, and urticarial rash 1. The joint-like pain is actually severe myalgia from larval muscle invasion 1.
Serum Sickness and Drug Reactions
Serum sickness-like reactions classically present with urticarial rash, migratory polyarthralgia/arthritis, fever, and gastrointestinal symptoms occurring 7-21 days after drug or biologic exposure 2. This represents a Type III hypersensitivity reaction.
Other Rheumatologic Conditions
Urticarial vasculitis presents with urticarial lesions lasting >24 hours, arthralgia/arthritis, and systemic symptoms including gastrointestinal involvement 2. Unlike simple urticaria, lesions are painful rather than purely pruritic and leave residual hyperpigmentation 2.
Adult-onset Still's disease features salmon-pink macular rash (often evanescent), migratory polyarthritis, fever, and gastrointestinal symptoms 2. The rash typically appears with fever spikes.
Critical Diagnostic Features to Elicit
Temporal Pattern
- Episodic vs. continuous symptoms: Autoinflammatory syndromes have distinct attack patterns with symptom-free intervals 1
- Duration of fever episodes: MKD typically 4-6 days, TRAPS often longer (>7 days) 1
- Timing relationship: Hookworm shows weeks between rash (ground itch) and GI symptoms 1
Rash Characteristics
- Migratory vs. fixed: TRAPS characteristically has migratory rash 1
- Urticarial vs. maculopapular: Helps distinguish between conditions 1, 2
- Duration of individual lesions: Urticarial vasculitis lesions persist >24 hours 2
- Associated findings: Periorbital edema suggests TRAPS or trichinellosis 1
Joint Involvement Pattern
- Truly migratory (moving from joint to joint): TRAPS, serum sickness, rheumatic fever 1, 2
- Additive polyarthritis: More typical of Still's disease 2
- Myalgia vs. arthralgia: Trichinellosis causes severe myalgia, not true arthritis 1
Exposure History
- Barefoot walking on soil/sand: Hookworm 1
- Raw/undercooked pork consumption: Trichinellosis 1
- Recent medication or biologic therapy: Serum sickness 2
- Travel to endemic areas: Various parasitic infections 1
- Family history of periodic fevers: Autoinflammatory syndromes 1
Diagnostic Workup Algorithm
Initial Laboratory Assessment
- Inflammatory markers during symptoms: ESR, CRP, CBC with differential (eosinophilia suggests parasitic infection or autoinflammatory disease) 1
- Serum amyloid A (SAA): Elevated in autoinflammatory syndromes 1
- Creatinine kinase: Markedly elevated in trichinellosis 1
Pathogen-Specific Testing
- Concentrated stool microscopy (three samples): For hookworm and other helminths 1
- Serology for Trichinella: If appropriate exposure history, though seroconversion takes 3-5 weeks 1
- Eosinophil count: >3 × 10⁹/L strongly suggests parasitic infection or autoinflammatory disease 1
Genetic and Immunologic Testing
- Genetic testing for autoinflammatory syndromes: TNFRSF1A (TRAPS), MVK (MKD), NLRP3 (CAPS) if episodic pattern present 1
- Complement levels (C3, C4): May be reduced in urticarial vasculitis 2
- Skin biopsy: Essential if urticarial vasculitis suspected—shows leukocytoclastic vasculitis 2
Common Pitfalls to Avoid
Do not dismiss episodic symptoms as functional: The periodic nature with complete resolution between episodes is pathognomonic for autoinflammatory syndromes and requires genetic testing 1.
Do not confuse myalgia with arthralgia: Trichinellosis causes severe muscle pain that may mimic joint pain, but true joint swelling is absent 1. Check creatinine kinase to distinguish.
Do not rely on single stool examination: Concentrated stool microscopy requires three separate samples for adequate sensitivity in hookworm detection 1.
Do not overlook medication history: Serum sickness can occur 1-3 weeks after drug exposure, and patients may not connect the temporal relationship 2.
Do not assume all urticaria is allergic: Urticarial lesions persisting >24 hours with systemic symptoms require biopsy to exclude urticarial vasculitis 2.
Age-Specific Considerations
In children, consider pinworm (Enterobius vermicularis) which causes intense pruritus ani, irritability, abdominal pain, and occasionally diarrhea, though joint symptoms are not typical 1, 3. Diagnosis requires the "sellotape test" applied to perianal skin 1, 3.
In adults with recent fish consumption, anisakiasis causes acute severe abdominal pain, nausea, and vomiting within hours, though the pruritic rash and joint symptoms would be atypical unless representing allergic manifestations 4.