Pachyonychia congenita (PC) is clinically seen with several distinctive features comprising a diagnostic triad of [1]:

• keratoderma;
• lingual leukokeratosis;
• hypertrophic nail dystrophy.

Although these components are most common, elements of the triad may be absent in some patients, making it an optional diagnostic instrument. As PC is associated with mutations in keratin genes, the affected areas are located in places abundant in keratinization, particularly, soles of the feet. PC in such location gives rise to painful and crippling lesions of keratoderma linked with repetitive blistering in the callus [2]. The pain is related to secondary infections, pressures in the nerve endings and blister fluid accumulation under the epidermis of callus [3].

Dystrophic nails can vary in appearance between family members thought to carry the same mutation. The nails usually appear hypertrophied, discolored with atypical angulation on the nail bed. The presence of these abnormalities can be spared in some nails, affecting only the specific ones, most commonly on the toes [2].

Those afflicted with PC also present with cystic processes in the epidermis like follicular keratosis or pilosebaceous cyst formation [2]. These can be located over the entire body although most typical sites are the neck, face, back, abdomen, and buttocks [4]. A classification of PC in two types (PC-1 and PC-2) was dependent on the presence of these pilosebaceous cysts and other features but in time could not survive criticism [5]. Thus a new classification based on the mutant gene came into existence. Modern grouping contains four subclasses of PC, which are PC-6a, PC-6b, PC-16, and PC-17 each based on mutations encoding K6a (for the PC-6a subtype accordingly) or other proteins [2].

Diffuse hair loss or alopecia can accompany PC [6].

• Pain

  Present work addresses the degree to which the protein profile is altered in the epidermis where the severe pain originates. [ucdavis.pure.elsevier.com]

  The pain is usually constant by age 10.4 Many adults with PC rely on canes, crutches or wheelchairs or even resort to crawling on their knees to avoid increased plantar pain by walking. [the-dermatologist.com]

  The highly visible nail changes and painful plantar thickening exert a psychosocial effect on most affected adolescents. [scholars.northwestern.edu]

  […] toenails and fingernails, pilosebaceous cysts, palmoplantar hyperhidrosis, hoarseness, pili torti, and natal teeth. 2 Treatment alternatives for painful hyperkeratoses have met with limited success due to short-term mitigation and high recurrence rates [journals.lww.com]

  […] w/plantar keratoderma 2 Often require medication for pain 65 (24%) 12 (18%) 5 (26%) 74 (31%) 19 (18%) 175 (25%) Very painful, but do not use medication 114 (43%) 32 (47%) 11 (58%) 111 (46%) 34 (33%) 302 (43%) Somewhat painful 77 (29%) 24 (35%) 3 (16% [ncbi.nlm.nih.gov]

• Disability

  disability claims, etc. [pachyonychia.org]

  Successful targeted therapies are currently lacking for this oftentimes disabling disorder. [ncbi.nlm.nih.gov]

  Type 4 patients (keratin-6B gene mutations), in addition to type 1 findings, also present with laryngeal lesions, hoarse voice, intellectual disability, and alopecia. These patients account for 7% of PC cases. For more information, see OMIM. [visualdx.com]

• Falling

  Treatment options for PC fall into four broad categories: (1) Non- invasive (mechanical) e.g. abrasion with some hand tool (2) Invasive (surgical) e.g. electrofulgration, excision (3) Chemical methods using urea, propylene glycol, alpha hydroxy acid [edoj.org.eg]

  Motivation and Support When you are dealing with unhealthy eating patterns it can become increasingly difficult to change habits and fall back into healthy eating. [thefreshcarrot.ca]

  Research is now moving forward to the next study scheduled for Fall 2012. [best-charities.org]

  In the Fall of 2012, physicians asked PC Project to collect data from patients in the IPCRR who had nails removed. There are many questions regarding both the methods of nail removal and the outcome for PC patients. [pachyonychia.org]

  Treatment Treatment options for PC fall into four broad categories: Non-invasive (mechanical) e.g. abrasion with some hand tool Invasive (surgical) e.g. electrofulgration, excision Chemical methods using urea, propylene glycol, alpha hydroxy acid Pharmacological [ncbi.nlm.nih.gov]

• Surgical Procedure

  It can also improve spontaneously in a period of several years. 1,3,4,8,10 Surgical procedures to improve voice quality should be avoided, because they can makes the underlying condition worse. 1 Keratins 6, 16 and 17 are in response to stress. [elsevier.es]

  The surgical procedures are repeated as necessary to maintain an open airway; however, surgical procedures to the larynx aimed at improving hoarseness should be avoided as they may tend to worsen the condition. Cysts. [ncbi.nlm.nih.gov]

• Nail Abnormality

  Pachyonychia congenita type I is an autosomal dominant disorder where nail abnormalities are a constant feature and develop during childhood. [ncbi.nlm.nih.gov]

  We studied three families suffering from nail abnormalities who had previously been diagnosed as pachyonychia congenita. No keratin gene mutations were detected. [rug.nl]

  Diagnosis The diagnosis may be suspected if a young child has extensive nail abnormalities including thickened nail beds and unusually formed nail plates. [socialstyrelsen.se]

• Pneumonia

  Preliminary research reports that selenium may be beneficial in the prevention of several types of infection, including recurrence of erysipelas (bacterial skin infection associated with lymphedema) or Mycoplasma pneumonia. [simplygoodnaturalfoods.com]

• Nausea

  These sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding. [simplygoodnaturalfoods.com]

• Vomiting

  These sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding. [simplygoodnaturalfoods.com]

• Hypertension

  […] of these disorders there is also the apparent accumulation of fat in other regions of the body ;Metabolic abnormalities：insulin resistance, diabetes mellitus, hypertriglyceridemia, hepatic steatosis, acanthosis nigricans, polycystic ovarian disease, hypertension [max.book118.com]

  […] paraplegia 6 hereditary spastic paraplegia 73 hereditary spastic paraplegia 8 Hidrotic Ectodermal Dysplasia, Autosomal Recessive Hidrotic Ectodermal Dysplasia, Christianson-Fourie Type Holt-Oram syndrome Hooft Disease hyperferritinemia-cataract syndrome hypertension [rgd.mcw.edu]

• Thrombosis

  High-resolution US can be applied to examine the affected calluses for the fluid in blisters, thrombosis, and underlying vein lesions. Hyperkeratinization is characterized by hyperechoic linear and dotted areas. [symptoma.com]

• Pachyonychia

  […] in early childhood often suggests a diagnosis of pachyonychia congenita (PC). [scholars.northwestern.edu]

  Proteomic profiling of Pachyonychia congenita plantar callus. [ucdavis.pure.elsevier.com]

  Symmetrically thickened, dystrophic fingernails and toenails are the defining characteristic of pachyonychia congenita. There are two main clinical subtypes of pachyonychia congenita: Pachyonychia congenita-1 and pachyonychia congenita-2. [file.scirp.org]

  Report of the 16th Annual International Pachyonychia Congenita Consortium (IPCC) Symposium. IPCC Newsletter. Halladay, Utah: Pachyonychia Congenita Projec; 2019 Vol 16. Acceso 20 de febrero de 2020. [medicinaylaboratorio.com]

  Pachyonychia congenita with only nail involvement, J Dermatol 2006; 33(6): 437- 438. 8. Paller AS, Moore JA, Scher R. Pachyonychia congenital tarda: a late onset form of pachyonychia congenita, Arch Dermatol 1991; 127: 701- 703. 9. [edoj.org.eg]

• Nail Deformity

  The elevation is most pronounced distally, sometimes resulting in a pincer nail deformity. [jiaomr.in]

  This type of subungual hyperkeratosis leads to the elevation and increased transverse curvature of the nail plate. [4] The elevation is most pronounced distally resulting in an omega or pincer nail deformity. [ijpd.in]

  But at five years of age the patient had palmoplantar hyperhidrosis, and nail deformity was less severe. The right middle fingernail showed brownish pigmentation, and was thicker than other nails [Figure 3]. General examination was normal. [ijdvl.com]

  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 [escholarship.org]

  This type of subungual hyperkeratosis leads to the elevation and increased transverse curvature of the nail plate. The elevation is most pronounced distally resulting in an omega or pincer nail deformity. [ijhas.in]

• Ataxia

  […] septal defect 8 atrial heart septal defect 9 autoimmune lymphoproliferative syndrome type 2A autoimmune lymphoproliferative syndrome type 4 autosomal dominant Alport syndrome autosomal dominant centronuclear myopathy + autosomal dominant cerebellar ataxia [rgd.mcw.edu]

  图 9 T2WI 可见明显的延髓萎缩 [a] 伴轻度小脑萎缩 [a~b]，但脑桥基底部基本正常 [b]，四脑室稍扩大 [b]，中脑，特别是背侧，可见萎缩 [c]；l：矢状位 T1WI 可见典型的蝌蚪状脑干萎缩，包括明显的颈髓-延髓萎缩，脑桥基底部完整，需注意，中脑被盖萎缩同样促成了「蝌蚪」的形成 白质消融性白质脑病 白质消融性白质脑病（Vanishing white matter disease）又称为儿童共济失调伴中枢神经系统髓鞘化不良（childhood ataxia with central [neuro.dxy.cn]

• Stroke

  Forskningsprojekt Obstruktiv sömnapné är ett tillstånd med återkommande luftvägshinder under sömn som ökar risken för hjärt- och kärlsjukdom och stroke. Syndromet är även kopplat till allvarliga sjukdomar som diabetes, cancer och demens. [umu.se]

  Use cautiously with asthma or a history of ulcers or stroke. Avoid if pregnant. Children should not take doses larger than what is commonly found in foods. [simplygoodnaturalfoods.com]

• Headache

  Use cautiously with headache, hyperthyroidism (overactive thyroid), or if fair-skinned. Avoid if pregnant or breastfeeding. Black tea : Black tea is made from the dried leaves of Camellia sinensis, a perennial evergreen shrub. [simplygoodnaturalfoods.com]

• Insomnia

  CBD oil provides undisturbed sleep by preventing insomnia. Proper sleep is very much important for better health. Following are the benefits of CBD oil. It helps in reducing depression and anxiety. Provide undisturbed sleep at the night. [thefreshcarrot.ca]

Pachyonychia congenita is diagnosed clinically by the triad of dystrophic nails, keratoderma, and leukokeratosis on the buccal or lingual mucosa.

A biopsy can be taken from a hyperkeratotic area and observed in a light microscope where acanthosis and orthokeratosis may be seen. Immunohistochemistry with the addition of antibodies can be useful [7] [3].

Genetic studies are performed with an objective to educate the patient about the specifics of PC and to collect data for research in order to find the best treatment for a particular mutation [8]. These exams involve the amplification of affected genes utilizing a quantitative reverse transcription-polymerase chain reaction (RT-PCR). Mutations in four types of genes responsible for the synthesis of K6a, K6b, K16, and K17 proteins are noted [3].

Some examinations radiologic like ultrasonography (US) can be useful to follow the dynamics of the disease. High-resolution US can be applied to examine the affected calluses for the fluid in blisters, thrombosis, and underlying vein lesions. Hyperkeratinization is characterized by hyperechoic linear and dotted areas. Fluid will be seen as anechoic and situated under the epidermis [1].

In those cases with markedly altered protein levels, monitoring the callus profile may provide an objective measure of treatment efficacy. [ucdavis.pure.elsevier.com]

Treatment Currently there is no specific therapy for PC so the main aim of treatment is to alleviate the pain caused by the plantar keratoderma. [the-dermatologist.com]

Mechanical treatments such as filing, grinding, cutting, and clipping of affected nails are somewhat effective in reducing symptoms in mild cases. 1 Reports of surgical management are sparse in the literature. [journals.lww.com]

A treatment protocol for botulinum toxin injections in the treatment of pachyonychia congenita-associated keratoderma. Br J Dermatol 2020;182:671-677. https://doi.org/10.1111/bjd.18169. [medicinaylaboratorio.com]

RESULTS: Patients reported surgical treatments being most effective for cysts and mechanical treatments the most effective conventional therapeutic approach for all other investigated manifestations. [ncbi.nlm.nih.gov]

Knowledge of the exact gene defect is likely to assist in predicting disease prognosis and clinical management. [ncbi.nlm.nih.gov]

Prognosis - Pachyonychia Congenita Not supplied. Treatment - Pachyonychia Congenita Not supplied. Resources - Pachyonychia Congenita Not supplied. [checkorphan.org]

Prognosis Complications may include secondary infection that is usually well controlled by antibiotics therapy. [orpha.net]

–10,000 cases have been reported worldwide. [10] Sex Pachyonychia congenita affects both sexes equally. [5, 11] Age Patients with pachyonychia congenita often present at birth or soon after with the characteristic hypertrophic toenail dystrophy. [5] Prognosis [emedicine.com]

Etiology Although historically two subtypes have been described, PC-1 and PC2, it is today recommended to classify PC patients into four subgroups based the underlying molecular etiology: PC-K6a, PC-K6b, PC-K16 and PC-K17, as PC is caused by dominant [orpha.net]

Some authors propose that steatocystoma multiplex is simply a variant of pachyonychia congenita type 2 because they both share the same underlying etiology. [diki.pl]

GENETIC CAUSES OF PACHYONYCHIA CONGENITA Etiology & Pathogenesis 1/31/2015 Prepared by Dixi Dawn F. Apigo 10. [slideshare.net]

However, indi¬vi¬duals with¬out these recogni¬zed traits and conditions also develop OSA making the etiology and pathophysiology unclear. [umu.se]

The discussion covers the phenotype spectrum, epidemiology, mode of inheritance, pathogenesis, and clinical profile of each condition, all of which is accompanied by a wealth of illustrations. [books.google.com]

Summary Epidemiology The prevalence is not known but approximately 1000 patients have been registered to date worldwide. Clinical description PC presents clinically as a spectrum of conditions. [orpha.net]

Any secondary infection may need to be treated with antibiotics, though infection can often be prevented with appropriate grooming and vinegar or bleach baths.[12][1][7] Epidemiology[edit] Pachyonychia congenita is a rare disorder with an unknown prevalence [en.wikipedia.org]

[…] few months of life. [1] [3] :569 Signs and symptoms Common symptoms include: Excess keratin in nail beds and thickening of the nails Hyperkeratosis on hands and feet Oral lesions that look like thick white plaques Steatocystoma multiplex Pain Blisters Pathophysiology [ipfs.io]

Pathophysiology The condition is caused by genetic mutations in one of four genes that encode keratin proteins specific to the epithelial tissues affected in the two forms of the disorder. [wikidoc.org]

However, indi¬vi¬duals with¬out these recogni¬zed traits and conditions also develop OSA making the etiology and pathophysiology unclear. [umu.se]

Pathophysiology Keratins are key structural proteins that form the cytoskeleton of epithelial cells. They are classified based on their biochemical properties into either type I (K9-K28, K31-K40) or type II keratins (K1-K8, K71-K86). [emedicine.com]

Efforts to decrease skin friction and moisture may also improve and/or prevent transgrediens spread. [ncbi.nlm.nih.gov]

Sirolimus oral solution and tablets have been used to prevent kidney transplant rejection since 2001. The effects of this medicine have been evaluated in experimental models. [ema.europa.eu]

Tea tree oil : Tea tree oil is purported to have antiseptic properties, and has been used traditionally to prevent and treat infections. [simplygoodnaturalfoods.com]

Unfortunately, the pain associated with injections into lesions (oral pain medication and regional nerve blocks were required to allow treatment), prevents widespread use of this mode of administration. [sbir.gov]

1. Van Steensel MAM, Coulombe PA, Kaspar RL, et al. Report of the tenth annual International Pachyonychia Congenita Consortium meeting. J Invest Dermatol. 2014;134(3):588-591.
2. WHI McLean, CD Hansen, MJ Eliason, FJD Smith.The Phenotypic and Molecular Genetic Features of Pachyonychia Congenita. J Invest Dermatol. May 2011;131(5):1015–1017.
3. Cao Y-A, Hickerson RP, Seegmiller BL, et al. Gene Expression Profiling in Pachyonychia Congenita Skin. J Dermatol Sci. 2015;77(3):156-165.
4. Rathore PK, Khullar V, Das A. Pachyonychia Congenita Type 1: Case Report and Review of the Literature. Indian J Dermatol. 2016;61(2):196-199.
5. Wilson NJ, Leachman SA, Hansen CD. A large mutational study in pachyonychia congenita. J Invest Dermatol. 2011 May;131(5):1018-24.
6. Nikoo A. Pachyonychia Congenita-Associated Alopecia. Case Rep Pathol. 2012:850658.
7. Rathore PK, Khullar V, Das A. Pachyonychia Congenita Type 1: Case Report and Review of the Literature. Indian Journal of Dermatology. 2016;61(2):196-199.
8. Wilson N, O’Toole E, Milstone L, et al. The molecular genetic analysis of the expanding pachyonychia congenita case collection. Br J Dermatol. 2014;171(2):343-355.