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What is Pachyonychia Congenita? Dr. Sancy Leachman has provided this definition based on the literature and multiple text resources -- "A rare, hereditary, autosomal dominant palmoplantar keratoderma. Currently two distinct syndromes of PC are recognized: PC-1, or Jadassohn-Lewandowsky type, and PC-2, or Jackson-Lawler type. The most common and prominent features of the syndromes include hypertrophic nail dystrophy, focal palmar and plantar hyperkeratoses, follicular hyperkeratosis, leukokeratosis of the oral mucosa, steatocystoma, and pilosebaceous cyst formation. Most data suggest germline mutations in keratins K6a and K16 are associated with PC-1 and mutations in keratins K6b, and 17 are associated with PC-2." A few other related disorders are sometimes incorrectly diagnosed as PC but appear to be caused by mutations in other genes. PC is often listed with other scaly skin disorders. In addition to PC (Pachyonychia congenita), this group of related inherited disorders includes ichthyotic conditions, epidermolysis bullosa and palmoplantar keratodermas. Clinical Trial February 2008 Essay "PC Clinical Trial" by Mary Schwartz UPDATE April 24, 2008: Today was the last scheduled injection date for the TD101 PC Clinical Trial. However, the trial is being continued for a few weeks. Dr. Leachman will present information on the trial at the upcoming IPCC meetings and we will post a summary of the data when available. GENETICs and PC PC is a genetic disorder and follows an autosomal dominant pattern. We have prepared a very Simplified Explanation of Genetics in PC. Males and females are equally affected. No pattern of occurence has been found as to ethnicity or nationality. The possibility of transmission of the mutated copy of the gene for PC is 50% for each pregnancy. The genes that are affected in PC involve several genes in a family of proteins called keratins. These proteins have critical function in the skin, nails and hair. The specific genes where mutations occur which cause PC are known as K6a, K6b, K16 and K17. A mutation on one of these genes that causes PC and PC symptoms. Keratins called K6a-K16 and K6b-K17 are considered “keratin pairs” because they specifically interact with each other. This is also why a mutation in just one of the two genes can cause PC as the mutation changes the way the two proteins interact. The mutations on the keratin genes occur at different locations along the gene. Through genetic testing the specific mutation site is determined. The PC Keratin Chart is a graphic illustration of the four keratine genes with the locations of the mutations identified as of February 2005. Additional Information on Genetics and PC For Patients (Mar 2005), PC Project Brochure
Genetics Home Reference (National Institutes of Health)
DNA From the Beginning TYPES OF PC The majority of research findings identify two types of pachyonychia congenita: Type 1 (also known as Jadassohn-Lewandowsky) appears to be caused by mutations in keratins K6a and K16 (Bowden PE, et al., 1995; Lin MT, et al., 1999; McLean WH, et al., 1995; Smith FJ, et al., 1999, 1999 and 2000) and Type 2 (also known as Jackson-Lawler) appears to be caused by mutations in keratins K6b and K17 (Celebi JT, et al., 1999; Covello SP, et al., 1998; Kansky A, 2002; Smith FJ, et al., 1998). There may be additional forms that are presently not well defined. No specific gene mutation has yet been identified for several syndromes which may be related to PC including palmoplantar keratoderma, epidermolytic (EPPK), Tylosis or Unna-Thost syndrome and pachyonychia congenita tarda. In PC tarda, the symptoms are not present until the second, third or later decades of life. Importantly, not every affected individual displays every symptom. Each affected individual may display a unique set of signs and symptoms even within families. Therefore, Pachyonychia congenita may be difficult to diagnose because the signs and symptoms displayed vary as does the severity of a given symptom, and they frequently overlap between types. Because of the difficulty in diagnosing this disorder, Pachyonychia Congenita types are currently defined and determined by a combination of physical findings and genetic mutation testing. SYMPTOMS OF PC A careful study of all reported cases of Pachyonychia congenita (see Bibliography) as well as an evaluation of data gathered through the IPCRR (see PC Registry) indicates the following are symptoms consistently associated with Pachyonychia congenita.
Although some other symptoms have been reported to be associated with PC, and were previously listed on our website, the review of facts seems to indicate these other symptoms may not actually be related to PC, but may have been reported about another disorder or may simply be other unrelated symptoms of a person with PC. CURRENT THERAPIES There is no cure for PC at this time. Also, currently there is no therapy which is proven to successfully provide long term benefits. Nevertheless, we are learning that PC patients manage their PC in a variety of ways. These experiences and findings are listed in Patient-to Patient Tips. The most consistent report from patients is the need for frequent and consistent debridement of the hyperkeratoses whether done by the patient or by professionals. As the hyperkeratoses occurs as a reaction to trauma (stress or pressure), some patients have found ways to lesson the trauma to feet and hands through special shoes, canes, crutches, etc. The following publications list therapies which appear to be the most current. As additional information is gathered and research conducted, we hope that new effective therapies will become known.
Soaking the feet and hands in super saturated saline (salt) solutions followed by gentle debridement (scraping or rubbing off excess skin) and addition of 50% propylene glycol in water and encasement in plastic overnight at least weekly to soften and moisturize the tender skin. Nails are managed by a variety of means including: scraping or paring down the excess by manual means, or grinding off the excess with motorized sanding tools (like those used for small crafts). Soaking in a solution or application of cream containing 10-20% salicylic acid to soften the nails prior can sometimes be useful. Surgical removal of nails (ablation) and destruction of the nail matrix (where the nail originates) is a more permanent option, although it may need to be repeated if the matrix is not completely destroyed or removed. The following drugs are listed alphabetically. There is no present report of successful long term benefits from these treatments. Dilantin, which is an anti-epileptic agent that also prevents the breakdown of collagen and has been used for treatment of several ichthyotic disorders, including PC. Side effects can be prohibitive. For more information see eMedicine.com Emollients are used to keep the skin soft and moisturized. These may include heavy duty creams, unguents and Vaseline®. Fluorouracil, an antineoplastic agent which inhibits cell growth and proliferation, has also been prescribed with variable success. For more information see eMedicine.com Keratolytic agents, which cause calluses and thick horny skin to swell, soften, and then peel or scale off, have been commonly employed. These have active ingredients such as salicylic acid or glycolic acid. Lac-Hydrin is another product name in this category. For more information see eMedicine.com Oral retinoids, which regulate the differentiation and proliferation of epithelial cells have been prescribed with variable results. Some retinoids also possess antitumoral activity. Those frequently prescribed for PC include etretinate, isotretinoin and acitretin. For more information on retinoids please visit the following sites: Salicylic acid
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