Auto-inflammatory Diseases

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

It is very common for autoinflammatory diseases to present episodes of fever or rheumatic manifestations. It is also common for them to pretend to be autoimmune, infectious or neoplastic diseases. These disorders are hereditary and rare.

In autoinflammatory diseases, an abnormal activation of the innate immune system occurs. Unlike autoimmune diseases, it is not related to a T-cell response, nor is it characterized by high antibody production.

Let’s learn more about the main auto-inflammatory diseases.

Hereditary periodic fever syndromes

Hereditary periodic febrile syndromes are the most common form of autoinflammatory disease. Among these, the most frequent pathology is familial Mediterranean fever . It is characterized by recurrent and brief episodes of fever, as well as serositis or inflammation of the body’s serous tissues – pleura, pericardium and peritoneum.

In addition to the familiar Mediterranean fever,  there are other conditions that are part of this group. Are they:

• TNF receptor-associated periodic syndrome (TRAPS): presents with acute inflammatory episodes, with very high fever, muscle pain, rash on the trunk and extremities, and abdominal pain.
• Hyper-IgD syndrome and periodic fever: usually starts in the first two years of life and is characterized by high fever, swollen nodes in the neck, pain in the joints, muscles and abdomen, among others.

Cryopyrinopathies, one of the types of autoinflammatory diseases

They correspond to a group of rare autoinflammatory diseases  caused by the mutation of the NLRP3 gene. They include three pathologies :

• Familial cold autoinflammatory syndrome (FCAS):  appears in the first months of life and manifests with fever, urticaria, fatigue, headache, muscle and joint pain, and conjunctivitis. It is triggered by exposure to cold.

• Muckle-Wells Syndrome (MWS):  Symptoms are similar to FCAS, but episodes are longer lasting and recurrent. It also includes deafness, episcleritis (eye disease), and an increased risk of amyloidosis or abnormal accumulation of amyloid in organs or tissues.
• Chronic neurological, infantile and joint syndrome / NOMID Neonatal-onset systemic inflammatory disease (CINCA): is the most severe form of this type of syndrome. In addition to the symptoms of MWS, it causes meningitis, blindness, brain atrophy and bone deformities.

Pediatric granulomatous arthritis

This pathology is a subgroup of autoinflammatory diseases that are due to a mutation in the NOD2 gene. It is known by several names, but the most common are Blau syndrome  or  early-onset sarcoidosis . The only difference between the two is that in the first there is a family history and in the second there is no.

The main feature of this pathology is the presence of a persistent inflammatory state. It usually appears before 4 years of age and is commonly accompanied by arthritis, skin lesions, uveitis and fever in half of the cases.

Syndromes with pustular rash and episodic fever

This subgroup includes several typologies. Are the following:

• With inflammatory bone disease. It is a serious disease that appears in the first weeks of life and presents severe symptoms, similar to those of neonatal sepsis.

• Majeed’s Syndrome. It appears in the neonatal period and presents with symptoms such as multifocal osteomyelitis, pustular dermatitis and others. It’s very rare.
• With pyogenic arthritis. It is also called PAPA Syndrome and is characterized by appearing before 10 years of age and manifesting as arthritis and, in most cases, with pyoderma gangrenosum and severe cystic acne.
• With inflammatory bowel disease. It appears before the first year of life and is characterized by intestinal problems such as abdominal pain, bloody diarrhea, etc.
• With other manifestations. It includes DITRA, which appears before the age of 11 and is characterized by the appearance of skin lesions; and CAMPS, which includes psoriasis.

Syndromes with atypical neutrophilic dermatoses with lymphocytic infiltrate

This subgroup  includes three conditions:

• PRAAS (Proteasome-Associated Autoinflammatory Syndromes): its main characteristics 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:  there is a high fever and periodic rashes. Over time, lipomuscular atrophy also occurs in the upper body.

Syndromes with autoinflammation and immunodeficiencies

This subgroup  also includes three conditions:

• PLAID Syndrome. Cutaneous urticaria, erythema, and itching develop in response to cold, and there are additional immune defects.
• APLAID Syndrome. There are recurrent blisters on the skin and problems with the joints, eyes, intestinal tract and respiratory system.

• HOIL Syndrome. There is chronic auto-inflammation, in addition to invasive infections and muscle problems.