What Are Autoinflammatory Diseases?

Autoinflammatory diseases are rare and difficult to diagnose, as they often have similar characteristics to other diseases such as infections, autoimmune diseases, or cancer. Learn more about some of the common types in this article.
What Are Autoinflammatory Diseases?

Last update: 28 February, 2021

Autoinflammatory diseases, also known as “periodic syndromes”, are a type of condition characterized by periodic outbreaks of systemic inflammation. They affect the digestive system, neurological system, or skin. Also, they can affect soft tissues such as joints.

It’s very common for autoinflammatory diseases to involve episodes of fever or rheumatic manifestations. Also, it’s common for them to simulate autoimmune, infectious, or neoplastic diseases. Overall, these disorders are hereditary and rare.

In autoinflammatory diseases, there’s abnormal activation of the innate immune system. However, unlike autoimmune diseases, they don’t have to do with a T-cell response, nor do they involve a high production of antibodies.

Next, let’s get to know the main autoinflammatory diseases in more detail.

Hereditary periodic fever syndromes

A woman with a fever looking at a digital thermometer.

Hereditary periodic fever syndromes are the most common form of autoinflammatory diseases. Within these, the most frequent condition in familial Mediterranean fever. This involves recurrent and brief episodes of fever, as well as serositis or inflammation of the serous tissues of the body.

In addition to familial Mediterranean fever, other illnesses are also part of this group. These are:

  • TNF receptor-associated periodic syndrome (TRAPS): This involves acute inflammatory episodes, with very high fever, muscle pain, rash on the trunk and extremities, and abdominal pain.
  • Hyper IgD syndrome and periodic fever. It usually begins during the first two years of life and involves high fever, swollen glands in the neck, pain in the joints, muscles, and abdomen, among others.

Cryopyrinopathies, a type of autoinflammatory diseases

Next, cryopyrinopathies are a group of rare autoinflammatory diseases caused by mutation of the NLRP3 gene. Overall, they include three conditions:

  • Familial cold autoinflammatory syndrome (FCAS): It appears in the first months of life and presents itself in the form of fever, urticaria, fatigue, headache, muscle and joint pain, and conjunctivitis. Exposure to cold acts as a trigger.
  • Muckle-Wells syndrome (MWS): In this case, the symptoms are similar to those of FCAS, but episodes are longer-lasting and recurrent. It also includes deafness, episcleritis (eye disease), increased risk of amyloidosis, or abnormal accumulation of amyloid in organs or tissues.
  • Chronic infantile neurologic cutaneous and articular syndrome (CINCA) / Neonatal onset multisystem inflammatory disease (NOMID): This is the most severe form of this type of syndromes. In addition to the symptoms of MWS, it causes meningitis, blindness, brain atrophy, and bone deformities.

Pediatric granulomatous arthritis (PGA)

Next, this condition is a subgroup of autoinflammatory diseases due to a mutation in the NOD2 gene. It goes by several names, but the most common are Blau syndrome or early-onset sarcoidosis. The only difference between these two is that, in the former, there’s a family history and in the latter, there isn’t.

Overall, the main characteristic of this condion is the presence of a persistent inflammatory state. It usually appears before the age of 4 years and very often involves arthritis, skin lesions, uveitis, and fever in half of the cases.

Syndromes with rashes and fever

An elderly woman rubbing one hand with the other.

This subgroup includes several typologies, which are the following:

  • With inflammatory bone disease. This is a severe disease that appears in the first weeks of life and has severe symptoms, similar to those of neonatal sepsis.
  • Majeed syndrome. This appears in the neonatal period and presents symptoms such as multifocal osteomyelitis, pustular dermatitis, and others. It’s very rare.
  • With pyogenic arthritis. Also known as PAPA syndrome, it appears before the age of 10 and presents itself with arthritis and, in most cases, pyoderma gangrenosum and severe cystic acne.
  • With inflammatory bowel disease. Appears before the first year of life and involves intestinal problems, such as abdominal pain, bloody diarrhea, etc.
  • With other manifestations. Includes DITRA, which appears before 11 years of age and involves the appearance of skin lesions; and CAMPS, which includes psoriasis.

Syndromes with dermatoses and lymphocytic-like infiltrate

This subgroup includes three syndromes:

  • PRAAS (Proteasome-associated autoinflammatory syndromes): Their main features are skin abnormalities and lipodystrophy – partial or total absence of adipose tissue, or body fat.
  • CANDLE syndrome: Involves recurrent fever, almost daily, accompanied by skin lesions and developmental delay.
  • Nakajo-Nishimura syndrome: In this case, there’s high fever and periodic rashes. Eventually, there’s also lipo-muscular atrophy in the upper body.

Autoinflammatory and immunodeficiency syndromes

Again, this subgroup includes three entities:

  • PLAID syndrome. Cutaneous urticaria, erythema, and pruritus develop in response to cold and there are additional immunologic defects.
  • APLAID syndrome. There’s recurrent blistering of the skin and problems in the joints, eyes, intestinal tract. and respiratory system.
  • HOIL syndrome. There’s chronic autoinflammation, plus invasive infections, and muscle problems.

Of course, this is all very technical. However, we hope that it helps demonstrate the wide variety of these types of diseases and how they may manifest.

As always, if you have any questions, make sure to ask your doctor. 

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  • Aróstegui, J. I., & Yagüe, J. (2007). Enfermedades autoinflamatorias sistémicas hereditarias. Síndromes hereditarios de fiebre periódica. Medicina Clínica, 129(7), 267-277.