Caffey Disease - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Caffey disease, or infantile cortical hyperostosis, is an acute inflammatory disorder with sudden extra bone formation, usually in the long bones, chest ribs, jaw, and collarbone shaft. Hyperostosis - excessive formation of new bone is the characteristic feature of the disease. The condition often presents with fever, pain, and swelling in the joints in newborns at the time of birth or within a few months. They are a self-limiting condition, a rare genetic disorder, and the symptoms wane over time. However, some adults may have joint instability, shortened legs, hyperextensibility of skin, and a high risk of bone deformation and fractures.

Why Is It Called Caffey Disease?

Caffey's disease was first identified by Dr. John Caffey in 1945. He noticed unusual swelling in the hard and soft tissues of the children, causing pain and irritable behavior within a few months of birth. The X-rays showed a two to threefold increase in bone width in the affected area. The disease was termed infantile cortical hyperostosis, also known as Caffey disease, Caffey-Silverman syndrome, or De Toni Caffey disease. Worldwide, the incidence of Caffey disease is three per thousand children. Sometimes, the disease may go unnoticed since the symptoms resolve as the child grows.

What Causes Caffey Disease?

• Caffey disease presents with an unknown etiology, primarily attributed to genetic causes. The condition is inherited in an autosomal dominant fashion (only one copy of the varied gene from an affected parent may be sufficient to cause the disease).

• A mutation or alteration in the gene sequence of COL1A1 has been identified as the reason for Caffey's disease. The normal function of the COL1A1 gene is to instruct and monitor the synthesis of type I collagen (a structural and supportive protein found in bones, skin, connective tissue, cartilage, and tendons). The collagens are long fibrils surrounding the tissue cells interlinked and twisted like a twine. Collagens are classified into many types based on their structure and function. Of all, type I accounts for 90 percent (most abundant) of total collagen in the body.

• In Caffey disease, there is variation in the amino acid sequence of the COL1A1 gene. In particular, the position of the amino acid arginine is replaced with cysteine. The consequence of this mutation reflects an abnormal size and shape in the type I collagen fibrils.

How Does the Disease Progress?

• Time of Onset: Usually during the first few months of life, usually before the child reaches five months.

• Swelling and Thickening: During episodes, the affected bones—typically the collarbone, mandible (jawbone), and other long bones—may swell and thicken.

• Fever and Irritability: Fever, irritability, and general discomfort are frequently experienced during Caffey's disease episodes.

• Spontaneous Remission: Over time, the illness often gets better. By the time they are two or three years old, the majority of people with Caffey's disease no longer have any symptoms.

What Are the Symptoms of Caffey Disease?

The symptoms may vary from person to person. The reason is unknown, but some may persist with mild symptoms, and some suffer severely. Most of the major systems in the body are affected by Caffey disease. The following are a few symptoms associated with Caffey's disease.

• It thickened in the long bones' outer covering (periosteum) - Cortical hyperostosis.

• Skull bone thickening.

• Irregularities in the cortical bone.

• Infection and inflammation in the skin.

• Swelling in the joints and other areas.

• Muscle and joint pain.

• Behavior changes like crankiness and irritability.

• Increased sensitivity to touch and pressure.

• Fever and malaise.

• Breathing difficulty.

• Popping eyes.

• Abnormal curvature in the spine.

How Is Caffey Disease Diagnosed?

• History and Physical Examination: Family history is reviewed. During the physical examination, the clinician may visualize and palpate (feel by touch) the areas of swelling for tenderness. Neurological and other systems are evaluated for coordination.

• Genetic Testing: Genetic testing refers to DNA tests from blood, saliva, or other tissues to check for gene mutations causing Caffey disease.

• Radiographic Imaging: Widening and thickening of the bones are often noticed in radiological images.

• Laboratory Findings on Caffey Disease: Biochemical changes are observed in the body of a few affected children.

1. Blood samples show elevated levels of inflammatory markers like C-reactive protein, erythrocyte sedimentation rate, etc.

2. Anemia (low red blood cells) and thrombocytosis (high platelet count) have been encountered.

3. Biopsy of bone and muscle shows inflammatory reactions.

How Is Caffey Disease Treated?

• Evaluation-Based Treatment: Each child with Caffey disease presents with different clinical features. Thus, the treatment moves forward from the initial diagnosis. Symptomatic treatment for pain, swelling, infection, fever, or cranky mood involves the prescription of anti-inflammatories, analgesics (painkillers), and antipyretics (reduce body temperature).

• Genetic Counseling: The family members are given genetic counseling for a better understanding of the disease and to reduce their panic state. They may get clarified about the mode of inheritance, testing protocols, and risks and are guided in the proper management direction.

• Surveillance: A yearly health evaluation to check for joint stability, bone strength, dental status, skin conditions, and overall growth and development is necessary if the disease involves collagen disorders.

What Are the Differential Diagnoses of Caffey Disease?

• Prenatal Caffey disease or Caffey dysplasia is a variant without the involvement of the COL1A1 gene inherited in an autosomal recessive pattern.

• Bone-related changes can be suspicious of bone malignancies and osteomyelitis (bone infection). Biopsies and X-ray images are used to differentiate them from Caffey's disease.

• Childhood traumas (physical abuse) may show similar signs of fractures and physical injuries.

• Hypervitaminosis A (bone pain and swelling), prostaglandin exposure (bone thickening), hyperphosphatemic familial tumoral calcinosis (abnormally high serum phosphate levels and bony changes), and storage disease have to be ruled out.

Conclusion:

Caffey disease is a self-limiting condition. Diagnosis is usually based on clinical features, such as the pattern of bone involvement and the age of onset. Imaging studies, such as X-rays, may be used to visualize the bone changes. The treatment involves coordinating an interdisciplinary team and compliance from parents or caretakers. Managing symptoms with medications, dietary changes, physical and speech therapy, and supportive care will decrease distress and improve the quality of life.