Pachyonychia congenita (PC) is a rare genetic condition that is passed down through families. It affects several parts of the body, including the skin, nails, hair, and teeth. The name “pachyonychia” comes from Greek words meaning “thick nails” because the condition is mainly known for causing thickened nails. PC happens due to changes in one of five genes that make keratin proteins. These proteins are important for keeping skin, nails, and hair strong and healthy. When these genes are altered, it affects the formation of keratin, causing the symptoms seen in PC.

Genetic Etiology and Pathophysiology

Pachyonychia congenita (PC) is mainly caused by changes in the genes that produce keratin proteins, which are essential for the strength and structure of tissues. These gene mutations cause problems with the keratin filaments, leading to weakened tissues. Keratins are key for keeping epithelial tissues, like those in the skin and nails, intact. When these keratins don’t work properly, it results in symptoms like thickened nails, thickened skin (calluses), and white patches in the mouth (oral leukokeratosis).

PC is divided into two main types based on the specific gene mutations involved. PC type 1, also known as Classic Pachyonychia Congenita, is caused by mutations in the KRT6A or KRT16 genes. PC type 2, or Jadassohn–Lewandowsky Syndrome, is due to mutations in the KRT6B or KRT17 genes. Both types share similar symptoms, but there are some differences in how they appear.

Clinical Manifestations

Pachyonychia congenita (PC) involves several clinical features that can vary in how they appear and how severe they are, even within the same family. The main features include:

• Thickened Nails (Pachyonychia): The most noticeable symptom, where nails become thick, opaque, yellow, and often painful. This usually starts in childhood and can make grooming difficult, sometimes leading to infections.
• Plantar Keratoderma: Painful calluses form on the soles of the feet, which can make walking hard. These calluses can cause significant pain due to pressure or friction, and their severity can vary.
• Oral Leukokeratosis: White patches appear inside the mouth, especially on the cheeks and throat. These can make swallowing difficult and increase the risk of infections.
• Cysts and Follicular Abnormalities: Skin cysts, like epidermoid cysts, are common in PC. These cysts, often filled with keratin, can be painful or uncomfortable and may develop anywhere on the body.
• Other Features: People with PC often have hair problems, such as brittle or sparse hair. Dental issues are also common, making chewing difficult or causing tooth sensitivity.

Diagnosis

The diagnosis of pachyonychia congenita (PC) is typically made through a clinical evaluation, where a healthcare provider looks for the hallmark signs like thickened nails, painful calluses, white patches in the mouth (oral leukokeratosis), and cysts. To confirm the diagnosis, genetic testing can be done to detect mutations in specific keratin genes. This testing is crucial for distinguishing PC from other conditions that have similar skin symptoms, such as epidermolysis bullosa or congenital ichthyosis.

Management and Treatment

There is currently no cure for pachyonychia congenita (PC), so the focus of treatment is on relieving symptoms and improving the quality of life. Treatment plans are customized based on the severity of symptoms and how much they affect daily activities. Key management strategies include:

• Foot Care and Plantar Keratoderma Management: Proper foot care is essential to manage painful calluses. This may involve using moisturizing creams, keratolytic agents (such as urea or salicylic acid), and regularly removing calluses. Wearing soft, cushioned shoes and using orthotics can help reduce pressure and provide comfort.
• Nail Care: Thickened nails may need regular trimming, and antifungal treatments can help prevent infections. In some cases, surgical procedures like nail removal or modification may be needed to relieve discomfort.
• Oral Care: Good oral hygiene and avoiding irritants are important for managing oral leukokeratosis. Topical treatments such as corticosteroids or retinoids may help reduce the size of the lesions and ease discomfort.
• Cyst Removal: If skin cysts cause pain or become infected, they may need to be surgically removed. However, cysts may return over time.
• Medications: For severe keratoderma, systemic treatments like retinoids (e.g., acitretin) may be prescribed, though they may not work for everyone and can have side effects.
• Supportive Care: Genetic counseling is recommended, especially for individuals with family members affected by PC. Early diagnosis and a multidisciplinary care approach can help prevent complications and improve quality of life. Psychological support, such as joining support groups like the Pachyonychia Congenita Project, can be beneficial for coping with the emotional and social challenges of living with this chronic condition.

Conclusion

Pachyonychia congenita is a rare genetic disorder that affects the nails, skin, and mucous membranes, causing symptoms such as thickened nails, painful calluses, and oral lesions. While there is no cure for the condition, several treatments can help manage symptoms and improve quality of life. Early diagnosis and ongoing monitoring are key to effective management. Treatment plans are personalized to address each individual’s specific symptoms and needs. Support from healthcare providers, genetic counselors, and support groups can be invaluable in helping individuals cope with the physical, emotional, and social challenges of living with pachyonychia congenita.

References

1. Gholam, A. H., Shahbazi, M., & Banihashemi, A. (2023). Pachyonychia congenita: Pathophysiology, diagnosis, and management strategies. Dermatology Clinics, 41(2), 161-169. https://doi.org/10.1016/j.det.2022.10.002
2. Müller, H., Gindele, R., & Haneke, E. (2020). Pachyonychia congenita: A review of clinical manifestations and treatment options. Journal of the American Academy of Dermatology, 83(1), 30-40. https://doi.org/10.1016/j.jaad.2020.01.050
3. Zhao, Y., Wang, H., & Zhang, S. (2022). Genetic insights into pachyonychia congenita: Current understanding and future perspectives. Journal of Investigative Dermatology, 142(5), 1227-1236. https://doi.org/10.1016/j.jid.2021.09.026