Dermatology Online Journal
Pachyonychia congenita tarda affecting only the nails
- Author(s): Vaccaro, Mario
- Guarneri, Fabrizio
- Barbuzza, Olga
- Guarneri, Claudio
- et al.
Pachyonychia congenita tarda affecting only the nails1. University of Messina. Institute of Dermatology
Mario Vaccaro MD1, Fabrizio Guarneri MD1, Olga Barbuzza MD2, Claudio Guarneri MD1
Dermatology Online Journal 14 (2): 12
2. Institute of Occupational Health Policlinico Universitario, Messina, Italy. Vaccaro@unime.it
A 42-year-old woman presented with complaints of rapidly progressing thickening and yellowish discoloration of the nails for the past 24 months. All nails were affected and fingernails were more thickened than toenails. Her palms and soles were normal. Keratosis pilaris, palmoplantar blistering, hyperhidrosis, leukokeratosis, alopecia, dental malformation, corneal abnormalities and epidermoid cysts were absent. This patient has pachyonychia congenita tarda with clinical manifestations limited to nail involvement.
Pachyonychia congenita (PC) is a group of inherited disorders of epidermis and its appendages. Pachyonychia congenita can be divided into two main clinical subtypes, PC-1 and PC-2, and other rare variants, including PC-tarda in which the symptoms are not present until the second, third, or later decades of life. Mutations in keratins have been associated with PC, and the correlation between the mutated gene and the type of PC is generally consistent, causing fragility of mucosal epithelia, follicular keratinocytes, palmoplantar epidermis, or pilosebaceous units. Pachyonycia congenita with its different phenotypes is attributed to the formation of abnormal tonofilaments .
A 42-year-old woman presented with complaints of 24 months of rapidly progressing thickening and yellowish discoloration of the nails. She had received prolonged antifungal therapy, with no improvement. She denied itching, paronychial infections, increased sweating, cutaneous blisters, natal teeth, or ocular symptoms. There was no history of similar nail changes in any other family member in the last two generations and her parents were non-consanguineous.
|Figure 1. Typical nail changes of pachyonychia congenita: yellow-gray discoloration and thickening of nail plates, subungual hyperkeratosis, upward angulation of the nail and pincer nail deformity|
Examination revealed thickening and hardening with yellow-grey discoloration of all nail plates; hypercurvature on the transverse axis of the nail plates was present, giving a pinched shape to the free edges. All nails were affected, and fingernails were more thickened than toenails (Fig. 1). Her palms and soles were normal. Keratosis pilaris, palmoplantar blistering, hyperhidrosis, leukokeratosis, alopecia, dental malformation, corneal abnormalities and epidermoid cysts were absent. All hematological and biochemical investigations had normal results. Direct microscopic examination and cultures showed no fungal elements on repeated occasions. Nail plate biopsy was refused.
Pachyonychia congenita (PC) is a group of inherited disorders of epidermis and its appendages, which can be divided into two main clinical subtypes, PC-1 and PC-2 [2, 3], and other rare variants, including PC-tarda in which the symptoms are not present until the second, third or later decades of life [4, 5].
The most consistent and severe changes, usually developing in infancy, affect the nails, which appear symmetrical thickened, aberrantly shaped, and profoundly dystrophic; onset in the 4th or 5th decade has been also described [6, 7, 8]. Isolated early-onset nail change is very rare [9, 10, 11], and late-onset isolated nail dystrophy is even more unusual [12, 13]. Various other abnormalities such as palmoplantar keratoderma with thick callosities, oral leukokeratosis, angular cheilitis, hyperkeratotic follicular papules of the extremities, keratosis pilaris, hair abnormalities, hyperhidrosis, blister formation on feet and palms and corneal dyskeratosis are variably expressed. On the basis of the presence and prevalence of associated symptoms, numerous subdivisions of PC have been suggested and several clinical variants have been described [1, 2, 3].
Pachyonychia congenita should be differentiated from other focal palmoplantar keratodermas associated with oral leucokeratosis, congenital dyskeratosis, psoriasis, pityriasis rubra pilaris, congenital onychogryphosis, traumatic thickening of nails.
Treatment is palliative and frequently disappointing. The only effective treatment for nail lesions is radical excision of the nail, nail bed and nail matrix and skin implantation at the site of the removed nail. Emollients and keratolytic agents, antiseptic dressing, special shoes as well as topical and systemic retinoids are usually prescribed for skin lesions; for mucosal lesions, surgical or CO2 laser excision, removal of natal and neonatal teeth appeared to be useful .
Pachyonychia congenita syndromes, rare autosomal dominant keratin disorders, can be divided, not only clinically but also from a genetic point of view, in two main syndromes called PC-1 and PC-2. The first type is due to a mutation in genes encoding for keratin 6a (K6a) or keratin 16 (K16), the second is due to mutations in genes of keratin 6b (K6b) or keratin 17 (K17). Keratin genes include four consecutive parts, namely 1A, 1B, 2A and 2B, which encode for the alpha-helical rod domain of the proteins. Nearly all mutations reported for patients affected by PC are located at the terminal regions of the alpha helical rod domains, namely in the beginning of segment 1A and in the ending of segment 2B [4, 5, 15]. Only Connors et al.  have described a novel mutation in the central part of the 2B domain of K16 in a young girl with delayed-onset PC-1, while Xiao et al.  have reported a novel mutation in the second half of the 1A domain of K17 in a large pedigree with delayed-onset PC-2: in these cases, the authors speculate that the mutations in less critical sites of the keratins may explain the delayed onset of PC [16, 17]. It was generally supposed that the severity of the disease depends on the entity and position of the mutation (alterations at the extremities of the alpha-helical rod are harmful, because they do not allow the correct assembly of keratin molecules), but it has been demonstrated that people carrying the same mutation may have completely different clinical manifestations: there are many additional theories about the variability in expressivity of PC beyond environmental factors, such as modifying genes (including polymorphisms) and epigenetic factors (modification such as methylation of cytosines or alteration of proteins that bind DNA, thus changing the probability of transcription). Variation in severity may be in part also due to polymorphism in ancillary components of the cytoskeleton . More pedigrees of delayed-onset PC need to be studied to establish the correlation between the site of mutation in keratin and delayed-onset and severity of pachyonychia.
References1. McLean WH, Smith FJ, Cassidy AJ. Insights into genotype-phenotype correlation in pachyonychia congenita from the human intermediate filament mutation database. J Investig Dermatol Symp Proc 2005;10:31-6. PubMed
2. Feinstein A, Friedman J, Schewach-Millet M. Pachyonychia congenita. J Am Acad Dermatol 1988; 19: 705-11. PubMed
3. Leachman SA, Kaspar RL, Fleckman P, Florell SR, Smith FJ, McLean WH, Lunny DP, Milstone LM, van Steensel MA, Munro CS, O'Toole EA, Celebi JT, Kansky A, Lane EB. Clinical and pathological features of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10:3-17. PubMed
4. Paller AS, Moore JA, Scher R. Pachyonychia congenita tarda. A late-onset form of pachyonychia congenita. Arch Dermatol 1991; 127: 701-3. PubMed
5. Smith FJ, Liao H, Cassidy AJ, Stewart A, Hamill KJ, Wood P, Joval I, van Steensel MA, Bjorck E, Callif-Daley F, Pals G, Collins P, Leachman SA, Munro CS, McLean WH. The genetic basis of pachyonychia congenita. J Investig Dermatol Symp Proc 2005;10:21-30. PubMed
6. Lucker GP, Steijlen PM. Pachyonychia congenita tarda. Clin Exp Dermatol 1995; 20: 226-9. PubMed
7. Mouaci-Midoun N, Cambiaghi S, Abimelec P. Pachyonychia congenita tarda. J Am Acad Dermatol 1996; 35: 334-5. PubMed
8. Hannaford RS, Stapleton K. Pachyonychia congenita tarda. Australas J Dermatol 2000; 41: 175-7. PubMed
9. Dogra S, Handa S, Jain R. Pachyonychia congenita affecting only the nails. Pediatr Dermatol 2002; 19: 91-2. PubMed
10. Pryce DW, Verbov JL. A family with pachyonychia congenita affecting the nails only. Clin Exp Dermatol 1994; 19: 521-2. PubMed
11. Chang A, Lucker GP, van de Kerkhof PC, Steijlen PM. Pachyonychia congenita in the absence of other syndrome abnormalities. J Am Acad Dermatol 1994; 30:1017-8. PubMed
12. Nanda S, Grover C, Chaturvedi KU, Garg VK, Reddy BS. Pachyonchia congenita tarda with nail manifestations only. Pediatr Dermatol 2005; 22: 283-5. PubMed
13. Bansal A, Sethuraman G, Sharma V K. Pachyonychia congenita with only nail involvement. J Dermatol 2006; 33: 437-8. PubMed
14. Milstone LM, Fleckman P, Leachman SA, Leigh IM, Paller AS, van Steensel MA, Swartling C. Treatment of pachyonychia congenita. J Investig Dermatol Symp Proc 2005; 10:18-20. PubMed
15. Munro CS. Pachyonychia congenita: mutations and clinical presentations. Br J Dermatol 2001; 144: 929-30. PubMed
16. Connors JB, Rahil AK, Smith FJ, McLean WH, Milstone LM. Delayed-onset pachyonychia congenita associated with a novel mutation in the central 2B domain of keratin 16. Br J Dermatol 2001;144:1058-62. PubMed
17. Xiao SX, Feng YG, Ren XR et al. A novel mutation in the second half of the keratin 17 1A domain in a large pedigree with delayed-onset pachyonychia congenita type 2. J Invest Dermatol 2004; 4: 892-895. PubMed
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