Autoinflammatory syndromes (AIS)

Symptoms

The main symptom of many of the conditions included in the group is repeated episodes of fever, which spontaneously disappear after a few days, only to reappear again cyclically after a variable period of time. This fever is not caused by an infection and, therefore, does not respond to treatment with antibiotics or antiviral medication. Depending on the genetic defect, these conditions may be associated with a wide diversity of other manifestations, including skin, abdominal, joints, eyes or lungs.

Who is affected by the condition?

All the conditions within the group are infrequent and have an incidence of less than 5 cases per 10,000 inhabitants, for which reason they are considered to be rare conditions. The majority appear in infancy or adolescence.

Recent progress with research has clearly shown that some fevers where the cause is not found are provoked by a genetic defect.

Depending on whether or not they have a genetic cause, they can be classified as follows:

• Non-inherited periodic fever syndromes:
  • Systemic-onset juvenile idiopathic arthritis
  • PFAPA syndrome
• Inherited periodic fever syndromes:
  • Familial Mediterranean fever (FMF)
  • Hyper-IgD syndrome (HIDS)
  • Tumour necrosis factor receptor-associated periodic syndrome (TRAPS)
  • Cold-triggered familial autoinflammatory syndrome (CAPS):  familial cold autoinflammatory syndrome (FCAS), Muckle-Wells syndrome (MWS), CINCA syndrome.
• Systemic granulomatosis:
  • Blau's syndrome
  • Early onset sarcoidosis
• Autoinflammatory conditions associated with pyogenic lesions:
  • PAPA syndrome (sterile pyogenic arthritis, pyoderma gangrenosum and acne).
  • Deficiency of interleukin-1 receptor antagonist (DIRA)
  • Majeed syndrome
  • Cherubism
• Autoinflammatory diseases associated with proteosome defects:
  • CANDLE syndrome
• Type 1 Interpheronopathy
  • Aicardi-Goutières syndrome
  • Deficiency of Adenosine Deaminase 2 (DADA2)
  • Spondiloencondrodisplasia with autoimmune deregulation
  • SAVI syndrome
  • USP18 deficiency
  • X-linked reticulate pigmentary disease
• PLCG2 (phospholipase CG2) associated antibody deficiency and immune deregulation (PLAID)
• NLRC4-associated macrophage activation syndrome

Diagnosis

The diagnosis is based on the clinical features of each patient’s clinical picture. Blood tests are important in diagnosing the various autoinflammatory conditions, as they enable detection of the existence of inflammation. These analyses are repeated when the child is asymptomatic to see if they have normalised. Molecular or genetic analysis enables detection of the presence of mutations involved in the development of autoinflammatory conditions which are studied in patients suspected of suffering from them according to the features of the clinical picture. The diagnosis is confirmed when the patient shows evidence of being a mutation carrier and it is often necessary to study family members too.

Standard treatment

Treatment fundamentally depends on the type of condition and the response to the therapy chosen. For example, for familial Mediterranean fever, the treatment of choice is colchicine. Other treatments used on the various autoinflammatory conditions are cytokine inhibitors, such as IL-1 or the tumour necrosis factor α. Close monitoring of the patient is essential to prevent complications arising in the long term.