History
Thickened toenails, plantar keratoderma, and plantar pain are the 3 cardinal findings of pachyonychia congenita (seen in >90% of patients) and are present in most patients before age 5 years. [5, 6] Clinical differences among pachyonychia congenita subtypes include earlier onset and more frequent occurrence of nail dystrophy and keratoderma in pachyonychia congenita type K6a, concurrent fingernail and toenail thickening in pachyonychia congenita types K6a and K17, more palmar keratoderma in pachyonychia congenita type K16, more frequent occurrence of cysts in pachyonychia congenita type K17, follicular hyperkeratoses primarily in pachyonychia congenita type K6a, oral leukokeratoses most often in pachyonychia congenita type K6a, and natal teeth almost exclusively in pachyonychia congenita K17. [5, 6]
Thickened toenails
The development of thickened toenails in childhood is seen in almost all patients with pachyonychia congenita. [12, 5] The thickened nails often require constant paring and grooming to prevent overgrowth and trauma, and they may be accompanied by painful paronychia (both pressure related and infectious). In a large study, 249 of 254 (98%) patients reported toenail changes, involving an average number of 8.8 toenails (range 0-10, mode = 10). Patients with KRT6A mutations were 11.1 times as likely to have all 10 toenails affected than those with the KRT6B, KRT16, or KRT17 mutations. The characteristic thickened toenails typically develop early in life. This appears to be especially true for patients with KRT6A mutations whose age of onset averaged 0.35 years (or 4 mo) compared with those with KRT6B, KRT16, or KRT17 mutations (9.5 y, 6.8 y, and 0.9 y, respectively).
Keratoderma
Plantar keratoderma is the next most common finding of the disorder and occurs in 91-96% of patients. [12, 5] It typically develops in early childhood with the start of prolonged walking and weight bearing. It most commonly manifests as persistent large callouses on weight-bearing surfaces and may be preceded or accompanied by blistering. Fissuring and secondary infection may also occur. Palmar keratoderma is also often present, especially among patients with KRT16 mutations.
Plantar pain
The third most commonly encountered finding among patients with pachyonychia congenita is pain, mostly involving weight-bearing areas such as the plantar surfaces. In a large study, 89% of patients (225 of 254) reported pain. [5] Of note, plantar pain appears to be the most important feature to negatively impact quality of life among people with pachyonychia congenita and may be severe enough to result in limitation of activities or require medications to manage it. Evidence supports the possibility of a neuropathic source of at least some of the chronic pain in pachyonychia congenita. [13, 14]
Fingernail dystrophy
Fingernail dystrophy is also a feature of pachyonychia congenita, although slightly less consistently than toenail dystrophy. Thickened fingernails were reported in 220 of 254 (87%) patients in a large study. [5] The prevalence of fingernail changes appears to be highest in patients with KRT6A mutation. All of the 115 patients with KRT6A mutations and 40 (93%) of 43 with KRT17 mutations reported fingernail changes, whereas 56 (74%) of 76 with KRT16 and only 9 (45%) of 20 with KRT6B mutation carriers reporting affected fingernails. KRT6B mutation carriers were also found to have far fewer fingernails affected than the other mutations carriers.
Mucosal findings
Oral leukokeratotic plaques (which are not felt to be premalignant) are estimated to occur in approximately 70% of patients with pachyonychia congenita. [5, 12] They may be seen at birth or develop within the first year. The plaques are most commonly seen on the tongue and buccal surfaces of the mouth. In newborns, the leukokeratoses may lead to difficulties in suckling and breastfeeding. In a large study, 97% (115/115) KRT6A and 59% (45/76) KRT16 mutation carriers reported the finding compared with 7/20 (35%) KRT6B and 14/43 (33%) KRT17 mutation carriers.
Cysts
Historically, the presence of various pilosebaceous cysts, such as steatocystomas or vellus hair cysts, were thought to be a reliable distinguishing feature of pachyonychia congenita type II. [12, 15, 16, 17] In a large study, cysts of any type were reported in 104 of 254 (41%) patients. Cysts were reported in 38 of 43 (88%) patients with KRT17 mutation, in 11 of 20 (55%) KRT6B mutation carriers, in 47 of 115 (41%) KRT6A mutation carriers, and 8 of 76 (11%) KRT16 mutation carriers. [5]
Natal teeth
Natal or prenatal teeth are associated with pachyonychia congenita and present at birth or within the first 30 days of life. [12, 15, 18] They are typically lost in infancy and replaced with normal permanent teeth during childhood. Natal teeth may lead to trauma or lacerations of the infant’s tongue or mother’s breast during breastfeeding and can pose an aspiration risk in infancy They were previously reported to be a feature of pachyonychia congenita type 2. In a large study, 39 of the 254 patients reported natal teeth. Thirty six were KRT17 mutation carriers. Only 3 of 115 (3%) KRT6A carriers reported natal teeth, and none of the 96 patients with KRT16 or KRT6B mutation carriers reported natal teeth. [5]
Physical Examination
Nail dystrophy
Nail involvement usually demonstrates significant subungual hyperkeratosis and sometimes presents with premature termination of nail. The nails may grow to full length and have an upward-slanted or heaped-up appearance due to a progressive distal thickening, or the plate may terminate prematurely with a gently sloped distal edge of hyperkeratosis and exposed distal finger tip. The surface of the plate can be smooth or rough and is often discolored. Note the image below.
The most prominent feature is a substantially thickened, brownish gray nail plate with a rough surface.
Plantar keratoderma
The plantar keratoderma of pachyonychia congenita is typically symmetric and focal, developing in areas of friction, trauma, and weight bearing , although it may affect the entire plantar surface. Blisters, fissures, and open sores often develop within or adjacent to the calloused areas.
Follicular hyperkeratoses reminiscent of severe keratosis pilaris have been reported and are most frequently found on the elbows and knees and along the waistband area. Note the image below.
Hyperkeratotic lesions of the skin may involve acanthosis, hyperkeratosis, and parakeratosis.
Oral leukokeratosis
Leukokeratosis of the oral mucosa, as shown below, is seen as patchy whitish areas most commonly seen on the tongue and buccal mucosa. The gingival mucosa is rarely involved. The clinical appearance of the lingual and buccal leukokeratosis can resemble candidiasis and premalignant leukoplakia, respectively. Buccal lesions are often accentuated at areas of trauma such as along the bite line.
Leukokeratosis of the oral mucosa is a prominent sign. Patchy whitish areas may be seen on the back of the tongue; the buccal mucosa; and sometimes, the gingiva.
Natal teeth
Natal or prenatal teeth can generally be seen in a frontal position and are often friable and prone to caries.
Pilosebaceous cysts
Although various pilosebaceous cysts have been reported in pachyonychia congenita, steatocystomas and vellus hair cysts have been historically most associated. Steatocystomas present as numerous small skin-colored to yellow-colored cysts that range from a few millimeters to a few centimeters and typically occur in sebaceous gland–dense areas such as the chest, arms, armpit, and neck.
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The most prominent feature is a substantially thickened, brownish gray nail plate with a rough surface.
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Leukokeratosis of the oral mucosa is a prominent sign. Patchy whitish areas may be seen on the back of the tongue; the buccal mucosa; and sometimes, the gingiva.
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Hyperkeratotic lesions of the skin may involve acanthosis, hyperkeratosis, and parakeratosis.
