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Evaluation of the patient with autoinflammatory diseases

2026-04-15 - 15:49

Evaluation of the patient with autoinflammatory diseases

Lazăr Călin -University of Medicine and Pharmacy „Iuliu Hațieganu” Cluj-Napoca

Condition	Anamnesis + Physical Examination	Laboratory Tests	Imaging	Response to Treatment
PFAPA	Frequently begins before the age of 5, with perfectly regular febrile episodes every 28 days lasting 3–6 days, without symptoms between attacks and without long-term sequelae.Fever of 40–41°C (resolves within 1–2 days even without treatment), chills, oral and/or pharyngeal ulcers (lasting 3–5 days, healing completely), acute pharyngitis, and cervical adenitis.Absent (differential diagnosis): diarrhea, rash, arthritis, chest pain.	Required only for the differential diagnosis of certain acute infections.During flare-ups: leukocytosis, elevated CRP/ESR.	These are only required for the differential diagnosis of certain acute infections.	Prednisone 0.5–2 mg/kg/day in a single daily dose, at the onset of the flare, for 1–2 days.Partial tonsillectomy or adenoidectomy, after ENT consultation.
Familial Mediterranean Fever (FMF)	Monogenic autoinflammatory disease with autosomal recessive inheritance (MEFV gene), occurring in Mediterranean ethnic groups.Onset in 90% of cases before the age of 20; febrile episodes lasting 12–72 hours accompanied by gastrointestinal symptoms (abdominal pain, constipation/diarrhea, sometimes peritonitis with acute abdomen), articular manifestations (arthritis/arthralgia, myalgia), pleural involvement (pleuritic chest pain, pleural friction rub, decreased breath sounds), and cutaneous signs (erysipelas-like erythema).Between attacks – no clinical signs.	During attacks: elevated CRP/ESR, serum amyloid A (SAA), complement fractions, complete blood count, liver and kidney function tests (microalbuminuria = early sign of renal involvement).With nephrologist’s approval, renal biopsy in cases of renal involvement (amyloidosis).Periodic evaluation of adverse effects of biological therapy and colchicine.Genetic testing in tertiary centers.	Chest X-ray / chest CT in cases of suspected pleural involvement.Abdominal ultrasound in cases of suspected acute abdomen.	Risk of amyloidosis (especially renal).NSAIDs, ColchicineCanakinumab (anti-IL1β monoclonal antibody), with rheumatology approval.
TRAPS (Tumor Necrosis Factor Receptor–Associated Periodic Syndrome)	Autosomal dominant inheritance (TNFRSF1A gene).Periodic febrile episodes lasting more than 7 days (1–4 weeks), accompanied by migratory maculary–erythematous rash, myalgia, gastrointestinal manifestations (abdominal pain, constipation/diarrhea, sometimes peritonitis with acute abdomen), articular involvement (arthritis/arthralgia of large joints), ocular symptoms (conjunctivitis, periorbital edema), and serositis (peritoneal, pleural, or pericardial).	During attacks: elevated CRP/ESR, serum amyloid A (SAA), complement fractions, complete blood count (sometimes leukocytosis with thrombocytosis), and liver and kidney function tests.Acute-phase reactants may remain elevated between attacks.Genetic testing in tertiary centers.	Chest X-ray / chest CT in cases of suspected pleural involvement.Abdominal ultrasound in cases of suspected acute abdomen.ECG and echocardiography in cases of suspected pericarditis.	Short-term corticosteroid therapy, biological therapy (Etanercept, anti-IL1), in tertiary centers.
Mevalonate Kinase Deficiency (MVK)	Autosomal recessive inheritance of an enzymatic deficiency (MVK gene, located on chromosome 12).1. Severe form (Mevalonic Aciduria – MVA): facial dysmorphism (triangular face, prominent frontal bossing, hypertelorism), growth and neurological retardation, cataract, recurrent fever, neurological complications (cerebellar ataxia, hypotonia), early death.2. Moderate form (Hyper-IgD Syndrome with periodic fever – HIDS): onset at 6–12 months of age, attacks lasting 3–7 days separated by 1–2 asymptomatic months, sometimes triggered by immunizations, infections, or trauma. During attacks: high fever, chills, headache, gastrointestinal manifestations (abdominal pain, nausea, vomiting), cutaneous signs (erythematous–macular or purpuric rash), and occasionally oral/genital aphthae, cervical adenitis, arthritis/arthralgia, splenomegaly, and serositis.	Markedly elevated IgD levels (at least two determinations; normal values do not exclude the disease).Elevated urinary mevalonic acid levels during attacks.During attacks: leukocytosis, elevated CRP/ESR, serum amyloid, and IgA levels.	As indicated: abdominal ultrasound, brain MRI (in cases of neurological involvement).	NSAIDs, short-term corticosteroid therapy, IL-1β and TNF-α antagonists (initiated in tertiary pediatric rheumatology centers).
Familial Cold Autoinflammatory Syndrome (FCAS).Mild form of cryopyrinopathy (CAPS)	Familial cold intolerance (autosomal dominant inheritance), onset within the first 6 months of life.Exposure to low temperatures triggers after 1–2 hours: fever, chills, non-pruritic erythematous–macular rash, headache, nausea, intense thirst, arthralgia, and conjunctivitis – with rapid favorable evolution (12–24 hours), either spontaneously or after antipyretics and hydration.Between flare-ups, rash and myalgia may occur.Absent (for differential diagnosis): deafness, periorbital edema, lymphadenopathy, serositis.	During flare-ups: leukocytosis, elevated CRP/ESR, and serum amyloid levels.	For differential diagnosis only.	Mild or moderate forms do not require chronic treatment. Short-term corticosteroid therapy may be used at the onset of a severe attack. Biological therapies – only in severe forms of cryopyrinopathies, as determined in tertiary pediatric rheumatology centers.

Monitoring of autoinflammatory disease activity includes: physical examination, anthropometric indices, neurological and musculoskeletal assessment, and measurement of acute-phase reactants (leukocytes, CRP, sometimes serum amyloid). Home monitoring (patient diary) is performed using the activity index (AIDAI) with 13 parameters: fever >38°C, general symptoms, abdominal pain, nausea/vomiting, diarrhea, headache, chest pain, painful lymphadenopathy, arthralgia/myalgia, joint swelling, ocular manifestations, skin rash, and need for symptomatic medication. Each item is scored 0 (absent) or 1 (present), with a maximum daily score of 12. A score above 9 indicates active disease.