Differentials
Acute sarcoidosis
SIGNS / SYMPTOMS
Cough; dyspnea; chronic fatigue; wheezing; rhonchi; lymphadenopathy; photophobia; red, painful eye; erythema nodosum.
INVESTIGATIONS
CBC: anemia, leukopenia. Serum calcium: elevated. Angiotensin-converting enzyme level: elevated.
Chest x-ray: hilar and/or paratracheal adenopathy with upper lobe predominant, bilateral infiltrates; pleural effusions (rare) and egg-shell calcifications (very rare) may be seen.
Rheumatoid arthritis
SIGNS / SYMPTOMS
Age 50 to 55 years; more likely in females; active systemic arthritis lasting >6 weeks; most commonly affects bilateral metacarpophalangeal (MCP), proximal interphalangeal (PIP) and metatarsophalangeal (MTP) joints; rheumatoid nodules.
INVESTIGATIONS
Rheumatoid factor: positive. Anticyclic citrullinated peptide antibody: positive.
Joint x-ray: typical pattern of erosions.
Vasculitis
SIGNS / SYMPTOMS
Upper extremity and jaw claudication; headache and scalp tenderness; hematuria; asymmetrical brachial pulses; bruits; foot drop, wrist drop; cutaneous ulcers; palpable purpura.
INVESTIGATIONS
Erythrocyte sedimentation rate: >100 mm/hour. CRP: elevated. ANCA: positive.
Urinalysis: hematuria, proteinuria, red blood cell casts.
Biopsy of affected tissue: vessel wall necrosis, fibrinoid necrosis, karyorrhexis, and red blood cell extravasation.
Seronegative spondyloarthropathy
SIGNS / SYMPTOMS
Back pain; iritis; enthesitis.
INVESTIGATIONS
HLA B27: positive.
Joint x-ray: erosions. Ultrasound: enthesitis. MRI: bone marrow edema.
Acute appendicitis
SIGNS / SYMPTOMS
May be clinically indistinguishable.
Anorexia; right lower quadrant tenderness, guarding, and rebound tenderness.
INVESTIGATIONS
Abdominal CT and ultrasound: abnormal appendix (diameter >6 mm).
Acute abdomen
SIGNS / SYMPTOMS
May be clinically indistinguishable.
Involuntary guarding, reduced bowel sounds.
INVESTIGATIONS
Abdominal x-ray and CT: evidence of a different underlying cause.
Periodic fever, aphthous stomatitis, pharyngitis, adenitis (PFAPA)
SIGNS / SYMPTOMS
The most frequent cause of recurrent fever in children.
The key symptoms of PFAPA are those in its name: periodic high fever lasting 3-6 days at intervals of about 3-5 weeks, as well as aphthous ulcers, pharyngitis, and/or adenitis.[82][83]
Affects children with a disease onset before age 6 years, and resolves spontaneously with age (usually before puberty).
In between episodes, the children appear healthy.
At least 6 months of episodes.
Diagnosis requires recurrent negative throat cultures and exclusion of other causes (e.g., Epstein-Barr virus, cytomegalovirus).
INVESTIGATIONS
No distinguishing tests; distinction relies on precise clinical diagnosis.
Mevalonate kinase deficiency (MKD), also called hyperimmunoglobulinemia D syndrome (HIDS)
SIGNS / SYMPTOMS
Any ethnicity, but mostly Dutch and other European ancestry. Autosomal recessive.
Disease onset is typically in infancy. Attacks typically last 3 to 7 days and become less frequent and severe with age.
Severe pain with vomiting and constipation; symmetric arthritis; lymphadenopathy very common; splenomegaly occurs in almost half of children; cutaneous vasculitis is common; aphthous ulcers.
INVESTIGATIONS
Elevated amount of mevalonic acid metabolites in the urine during an attack. As MKD patients have normal mevalonic acid metabolites in between episodes, the diagnosis should be confirmed by measuring enzyme activity and/or analyzing DNA mutation.[60][84][85]
Serum IgD may be elevated. However, this is not specific or sensitive and could be elevated in other autoinflammatory syndromes, other chronic inflammatory conditions, and in children with mevalonate kinase deficiency (nearly half of whom will have persistently normal serum IgD levels).[86][87]
TNF receptor-associated periodic syndrome (TRAPS)
SIGNS / SYMPTOMS
The term TRAPS was coined in 1999 with the discovery that the disease-causing genes were identified on chromosome 12.[88] It is also known as familial Hibernian fever.[89]
Any ethnicity but mostly northern European. Autosomal dominant or sporadic.
Attacks typically last days to weeks and include migratory macules, patches, papules, and plaques; migratory myalgia; periorbital edema; pleurisy; conjunctivitis; scrotal pain. Amyloidosis occurs in 10%.
Cryopyrin-associated periodic fever syndromes (CAPS), including: familial cold autoinflammatory syndrome (FCAS); Muckle-Wells syndrome (MWS); neonatal-onset multisystem inflammatory disease (NOMID)/chronic infantile neurologic cutaneous and articular syndrome (CINCA)
SIGNS / SYMPTOMS
CAPS is an autosomal dominant inflammatory disorder encompassing a continuum of 3 phenotypes: FCAS, MWS, and NOMID (also called CINCA). These cryopyrinopathies were once thought to be distinct conditions, but are now used to describe disease severity.
Any ethnicity. Autosomal-dominant inheritance or sporadic.
FCAS: onset in early infancy and sometimes a few hours after birth. Cold or generalized cooling after sweating can trigger an attack. Urticarial itchy burning rash and arthritis during attacks. Rash starts on extremities then becomes generalized. Profuse sweating during attacks. Conjunctivitis and myalgias. Attacks <24 hours.
MWS: similar features to FCAS but more frequent attacks from several times per week to monthly and slightly longer duration. Distinguished from FCAS by the development of perceptive deafness and systemic amyloidosis (25%), which is rare in FCAS.
NOMID/CINCA: generalized urticaria-like eruptions and neutrophilic eccrine hidradenitis; intellectual disability; destructive arthritis; anterior uveitis, optic disc changes, and blindness; perceptive deafness.
Syndrome of pyogenic arthritis with pyoderma gangrenosum and acne (PAPA)
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