Dermatology Online Journal

Pachyonychia congenita tarda affecting only the nails
Mario Vaccaro MD¹, Fabrizio Guarneri MD¹, Olga Barbuzza MD², Claudio Guarneri MD¹
Dermatology Online Journal 14 (2): 12

1. University of Messina. Institute of Dermatology
2. Institute of Occupational Health Policlinico Universitario, Messina, Italy. Vaccaro@unime.it

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Abstract

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.

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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 [1].

Clinical synopsis

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
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.

Discussion

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 [14].

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. [16] 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. [17] 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 [15]. 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.

References

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