Background

CAPS are a group are disorders that have partly overlapping symptoms but share the same genetic cause. The conditions in the group will be three in number, Muckle-Wells syndrome (MWS), neonatal- onset multisystem inflammatory disorder, and familial cold autoinflammatory syndrome type 1 (FCAS1). Among these, FCAS1 is the mildest one, and MWS occurs with intermediate severity. The symptoms of CAPS include recurrent episodes of fever, joint pain that is particularly triggered by cold temperatures, rashes on skin, stressors, or fatigue. Such episodes last a few hours up to several days and generally have an infantile or early childhood onset. 

 Although the conditions comprising the CAPS spectrum share similar symptoms, each has its own distinctive patterns. Thise with FCAS1 are very sensitive to cold, so this can cause a painful or burning rash at first, which may then spread to the torso and limbs. In people with MWS, fever, joint pain, and skin rashes constitute most of the reactions to cold. They may also begin to have progressive hearing loss in their teenage years. MWS also includes kidney damage or skin lesions from abnormal deposits of amyloid. 

Epidemiology

This is a rare condition that has an estimated incidence of affecting two to five cases per one million individuals. However, it is believed that the condition is underdiagnosed because the features of CAPS are similar to those of other more common conditions. 

Anatomy

Pathophysiology

CAPS occurs due to gene mutations which leads to a defect in the cryopyrin protein, that plays a crucial role in controlling inflammation. CAPS are autosomal dominant diseases, meaning only one copy of the mutated gene from one parent is needed to cause the disease. Additionally, the gene can mutate instantaneously during conception, resulting in disease in children. 

Etiology

Mutation s in the NLRP3 gene causes CAPS. This gene produces cryopyrin protein which is a part of the NLR (“NOD-like” receptor) family that regulates inflammation in the immune system. Normally, the body sends signaling molecules and white blood cells to an injury to combat foreign invaders and repair damaged tissues. Cryopyrin plays a key role in assembling an inflammasome that initiates the inflammatory response. Researchers think that mutations in the NLRP3 gene, which cause CAPS, lead to an overactive cryopryin. This over activity results in inappropriate inflammatory responses, leading to fever episodes and damage to the body’s cells and tissues, which are characteristic of CAPS. 

Genetics

Prognostic Factors

Interleukin-1 inhibitors have been identified as effective treatment for children with CAPS, improving their long-term prognosis. Under treated or Untreated CAPS can lead to decreased quality of life, neurological damage, severe joint deformities, renal failure because of amyloidosis and deafness. 

Clinical History

The symptoms and signs can be noticed from birth in this condition which continues throughout the life. Along with swelling and rashes on the skin, affected people can have swelling, joint deformities like contractures that restrict movements, and joint inflammation. People suffering from NOMID usually complain of seizures, impaired cognition as a result of chronic meningitis, and headaches. Short statue, renal failure by amyloidosis, eye problems, and distinctive facial features are other characteristics of NOMID. 

Physical Examination

These include: 

1. Hearing test 

1. Examination of eyes 

1. MRI of inner ears and brain 

1. Genetic test 

1. Skin biopsy for rashes 

1. Testing joint fluid collected through puncture in lower spine. 

Age group

Associated comorbidity

• Hearing loss 
• Amyloidosis 
• Fatigue 
• GI issues 
• Growth retardation 
• Chronic asceptic meningitis 
• Urticaria 
• Recurrent rash 
• Chronic arthralgia 
• Arthritis 
• Uveitis 
• Conjunctivitis 
• Chronic systemic inflammation 
• Musculoskeletal problems

Associated activity

Acuity of presentation

Differential Diagnoses

• Familial Mediterranean Fever (FMF) 
• Hyper- IgD Syndrome (HIDS) 
• TRAPS (tumor necrosis factor receptor-associated periodic syndrome) 
• sJIA (Systemic Juvenile Idiopathic Arthritis) 
• MWS (Muckel Wells syndrome) 
• Adult-onset Still’s disease (AOSD) 
• NOMID 
• SLE 
• RA 
• PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and Adenitis) syndrome 
• Behcet’s disease 

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The treatment paradigm for Cryopyrin-Associated Periodic Syndromes (CAPS) focuses on controlling inflammation, preventing complications, and improving quality of life. Primary treatments include biologic agents that inhibit the interleukin-1 (IL-1) pathway, such as Anakinra, Canakinumab, and Rilonacept. Corticosteroids and NSAIDs are used for relief of acute systems, but long-term administration is usually avoided as there may be possible side effects. Symptomatic management involves specific therapies, monitoring and supportive care, patient education and support, a multidisciplinary approach, and participation in clinical trials. The goal should be to attain continued remission of symptoms, avoid long-term complications, and improve the quality of life for patients with CAPS. 

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Use of Il-1 inhibitors

Anakinra: It is an antagonist of IL-1 receptor that is indicated to lower the symptoms and decrease the damage of medial to severe RA and also indicated for treating NOMID and CAPS. 

Rilonacept: It is also an inhibitor of interleukin-1 receptor. 

Canakinumab: It is a monoclonal antibody that targets interleukin-1 beta, and indicated in the treatment of periodic fever syndroomes such as CAPS, FMF, and  sJIA. 

use-of-phases-of-management-in-treating-caps

CAPS is a chronic inflammatory disease that requires a multidisciplinary approach to manage. The disease is diagnosed through an initial assessment and diagnosis, which includes clinical evaluation, laboratory tests, imaging studies. Acute management involves control of symptoms with NSAIDS or corticosteroids and initiation of use of IL-1 inhibitors. Long-term maintenance includes sustained treatment, regular monitoring, and management of comorbidities. Education and support to patients are of paramount importance to psychosocial support. Palliative care focuses on alleviation of symptoms, improved quality of life, with a multidisciplinary approach involving patients, and families. Each phase requires a tailored approach based on individual patient needs and response to treatment. 

Medication

Future Trends

Media Gallary

References

Cryopyrin-Associated Periodic Syndromes: Otolaryngologic and Audiologic Manifestations – PMC (nih.gov)