Introduction
Pachyonychia congenita is a rare genodermatosis, first described in 1906 by Jadassohn and Lewandowsky.Reference Jadassohn and Lewandowsky 1 It characteristically affects the nails and palmoplantar surfaces, with the larynx less commonly involved.Reference Leachman, Kaspar, Fleckman, Florell, Smith and McLean 2 It is transmitted as an autosomal dominant trait, and is thought to affect between 5000 and 10 000 people worldwide.Reference Eliason, Leachman, Feng, Schwartz and Hansen 3
Pachyonychia congenita is caused by mutations in one of five keratin genes: KRT6A, KRT6B, KRT6C, KRT16 and KRT17. A new classification system now divides pachyonychia congenita into subtypes PC-K6a, PC-K6b, PC-K6c, PC-K16 and PC-K17, depending on the encoding genes affected.Reference Wilson, Leachman, Hansen, McMullan, Milstone and Schwartz 4 Keratins play an integral role in epidermal cell integrity and mechanical strength. Mutations in these five genes result in fragility of the epithelial cell cytoskeleton, which leads to cell cytolysis and subsequent hyperkeratosis.Reference McLean, Hansen, Eliason and Smith 5 – Reference McLean and Moore 7
The clinical manifestations of pachyonychia congenita normally present within the first three years of life,Reference Eliason, Leachman, Feng, Schwartz and Hansen 3 and include nail dystrophy, painful palmoplantar keratoderma, follicular hyperkeratosis and mucosal leukokeratosis.Reference Leachman, Kaspar, Fleckman, Florell, Smith and McLean 2 , Reference Eliason, Leachman, Feng, Schwartz and Hansen 3 Involvement of the larynx is a less common clinical feature. When affected, patients usually present with hoarseness and, much more rarely, laryngeal obstruction.
Pachyonychia congenita with laryngeal involvement has an unknown prevalence. Hoarseness has been reported with varying frequency in the literature. In 1987, Benjamin et al. found that hoarseness arose in less than 10 per cent of patients with pachyonychia congenita.Reference Benjamin, Parsons and Molloy 8 When Eliason et al. surveyed the clinical symptoms of 254 patients with confirmed pachyonychia congenita, patients were directly questioned about voice quality. In that cohort, hoarseness was present in 28 per cent of cases.Reference Eliason, Leachman, Feng, Schwartz and Hansen 3
We present the case of a 5-year old boy with pachyonychia congenita, subtype PC-K6a, who, from the age of 10 months, had repeated presentations with laryngeal obstruction following upper respiratory tract infections (URTIs).
Case report
A five-year-old boy was diagnosed with pachyonychia congenita at four weeks of age, when he presented with thickening of his fingernails (Figure 1) and oral plaques. This diagnosis was confirmed at nine months following genetic analysis, which showed a KRT6A gene mutation. Family history revealed he was born to non-consanguineous parents, and his mother, father and sister are all unaffected.
Fig. 1 Thickened fingernails.
The first symptoms of laryngeal obstruction began at 10 months of age, when he developed stridor, shortness of breath and increased work of breathing following a coryzal illness. He attended the local ENT department where he was intubated to stabilise his airway for transfer to a tertiary centre (Starship Children's Hospital, Auckland, New Zealand).
The patient underwent laryngoscopy and bronchoscopy, which revealed laryngeal obstruction due to vocal fold oedema and keratin plaques on the true vocal folds and epiglottis (Figure 2). The keratosis was debulked. After a failed trial extubation in the operating theatre, the patient remained intubated for 7 days in the paediatric intensive care unit, receiving antibiotics and steroids. He was discharged 3 days following extubation.
Fig. 2 Laryngoscopic view at first presentation.
Over the next year, the patient was admitted with stridor and increased work of breathing on two occasions; this was successfully managed with steroids and antibiotics. His voice was noted to remain hoarse in between attacks.
At two years of age, following a URTI, the patient presented locally with stridor and significant airway obstruction. He underwent laryngoscopy and bronchoscopy, which revealed large plaques of keratosis and oedema on both vocal folds causing near total airway occlusion. A tracheostomy was performed to secure his airway and he was transferred to Starship Children's Hospital. His tracheostomy was successfully decannulated after three weeks of treatment with antibiotics and steroids.
Over the next 18 months, the patient was admitted for two further periods of intubation for laryngeal obstruction. Both followed a URTI. After these multiple admissions, a decision was made to aggressively debulk each side sequentially in an attempt to achieve disease control (Figures 3–5). On each of these occasions, the potassium titanyl phosphate (KTP) laser was not only used to remove all visible keratosis on the larynx but also to debulk oedematous tissue.
Fig. 3 Laryngoscopic view before laser debulking.
Fig. 4 Laryngoscopic view three weeks following laser to left vocal fold.
Fig. 5 Laryngoscopic view after final sequential laser debulking.
This intervention was successful and there have been no further emergency presentations or requirement for intubation. Serial laryngoscopies, performed at four-monthly intervals, show a more stable larynx (Figure 6). The patient has some hoarseness, but a useful and easily intelligible voice.
Fig. 6 Laryngoscopic view one year following laser debulking.
Discussion
Pachyonychia congenita is a rare keratinising disorder that typically affects the nails and palmoplantar skin, but can also involve the hair, oral mucosa, tongue and larynx.Reference Leachman, Kaspar, Fleckman, Florell, Smith and McLean 2
Patients with a KRT6A mutation (as in our case) are more likely to have laryngeal involvement than those with other pachyonychia congenita subtypes.Reference Eliason, Leachman, Feng, Schwartz and Hansen 3 , Reference Shah, Boen, Kenner-Bell, Schwartz, Rademaker and Paller 9 Eliason et al. found that of the 71 patients who reported hoarseness, 69 per cent had KRT6A mutations, and, less frequently, KRT16 (21 per cent), KRT17 (14 per cent) and KRT6B (9 per cent).Reference Eliason, Leachman, Feng, Schwartz and Hansen 3 Shah et al. reported a higher proportion of their 17 patients with hoarseness having a KRT6A mutation, with a frequency of 82 per cent; 12 per cent of patients with hoarseness had a KRT17 mutation and 6 per cent had KRT16.Reference Shah, Boen, Kenner-Bell, Schwartz, Rademaker and Paller 9 No patients with KRT6B or KRT6C mutations reported hoarseness as a clinical symptom. This discrepancy may be accounted for by the different sample sizes.
The presence of hoarseness within the first year of life, with or without oral leukokeratosis, would suggest the diagnosis of a KRT6A mutation.Reference Leachman, Kaspar, Fleckman, Florell, Smith and McLean 2 , Reference Eliason, Leachman, Feng, Schwartz and Hansen 3 , Reference Shah, Boen, Kenner-Bell, Schwartz, Rademaker and Paller 9 This was demonstrated by Haber and Drummond, where the first presentation of hoarseness and signs of laryngeal obstruction was at nine months of age.Reference Haber and Drummond 10 Our patient presented with similar symptoms at a similar age. These are the only two reported cases of laryngeal obstruction where the diagnosis of subtype PC-K6a has been confirmed using mutational genetic tests.
Although laryngeal involvement is rare in patients with pachyonychia congenita, it has the potential to be life-threatening because of airway obstruction. There have been four other reported cases describing this complication in the literature.Reference Haber and Drummond 10 – Reference Wudy, Lenders, Pirsig, Mohr and Teller 13 Upper respiratory tract infection appeared to be a precipitating factor in developing airway compromise in our patient, who on each admission had preceding coryzal symptoms. This is the second report of a patient with a KRT6A mutation presenting with laryngeal obstruction following a URTI.Reference Haber and Drummond 10 Other cases of pachyonychia congenita, without genetic confirmation of subtype, have been reported by Wudy et al.Reference Wudy, Lenders, Pirsig, Mohr and Teller 13 and Cohn et al.,Reference Cohn, McFarlene and Knox 11 who described worsening airway symptoms in their patients following URTIs.
Given the variability of clinical presentation, which ranges from asymptomatic to sudden and acute airway obstruction, the management and treatment of pachyonychia congenita patients with laryngeal involvement is a challenging one, requiring a multidisciplinary approach. Early endoscopic evaluation of children with hoarseness is necessary to assess the airway and monitor disease progression. This is particularly important in patients younger than three years with a smaller laryngeal aperture, where hyperkeratosis can lead more quickly to airway compromise.Reference Wudy, Lenders, Pirsig, Mohr and Teller 13 Flexible nasendoscopy is a quick out-patient procedure that does not require a general anaesthetic, and is a useful tool in the initial assessment and surveillance of the larynx. Identifying the genetic subtype can also be helpful in predicting the potential risk of laryngeal involvement; for instance, those with subtype PC-K6a appear to be more susceptible, particularly at a young age.Reference Leachman, Kaspar, Fleckman, Florell, Smith and McLean 2 , Reference Eliason, Leachman, Feng, Schwartz and Hansen 3 , Reference Shah, Boen, Kenner-Bell, Schwartz, Rademaker and Paller 9 As was seen in our case and in others reported in the literature,Reference Haber and Drummond 10 , Reference Cohn, McFarlene and Knox 11 , Reference Wudy, Lenders, Pirsig, Mohr and Teller 13 URTIs can worsen symptoms; hence a lower threshold to admit these patients for observation and treatment may be advisable.
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• Pachyonychia congenita is a rare keratinising disorder, normally affecting nails and skin
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• Laryngeal keratosis is a less common occurrence, presenting as hoarseness or acute airway obstruction
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• Early endoscopy is essential in diagnosis and surveillance of the disease
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• Upper respiratory tract infections can exacerbate symptoms
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• Laryngeal manifestations of pachyonychia congenita respond well to aggressive laser debulking of hyperkeratosis and oedema
Conservative management is not the treatment of choice for pachyonychia congenita patients with airway obstruction; surgical intervention is needed to re-establish the airway.Reference Wudy, Lenders, Pirsig, Mohr and Teller 13 In earlier reports by Wudy et al.Reference Wudy, Lenders, Pirsig, Mohr and Teller 13 and Cohn et al.,Reference Cohn, McFarlene and Knox 11 microlaryngeal techniques were used to excise exophytic lesions, with good effect. More recently, Haber and Drummond described the use of carbon dioxide laser laryngoscopy on a nine-month-old girl who presented acutely with stridor and hoarseness.Reference Haber and Drummond 10 They carried out two laser treatments, one month apart, and the child remained symptom-free for just over two years. When features of laryngeal involvement returned at the age of three years, they were milder, and fewer deposits of hyperkeratosis, which were then removed by laser, were found on the larynx.Reference Haber and Drummond 10 We have found that using a KTP laser to aggressively debulk hyperkeratotic lesions and oedema of the larynx has kept our patient's symptoms and acute re-presentation under control. Prior to this, conservative management with steroids and antibiotics meant that the patient required periods of intubation on three occasions and a tracheostomy. Potassium titanyl phosphate laser laryngoscopy has been performed three times, resulting in a more stable airway, with no further intubations required.
Conclusion
Pachyonychia congenita can cause laryngeal keratosis, which can lead to hoarseness and progress to airway obstruction. When a child with pachyonychia congenita develops hoarseness or respiratory symptoms, we recommend early endoscopy to evaluate the larynx, and genetic analysis to determine the pachyonychia congenita subtype. The symptom of hoarseness in a child with pachyonychia congenita who is younger than 12 months would suggest the presence of a KRT6A mutation. Our experience indicates that the laryngeal keratosis and oedema typical of this condition respond well to aggressive KTP laser debulking. This article will increase awareness of the laryngeal manifestations of pachyonychia congenita and provide a framework for a management strategy.
