Pachyonychia Congenita 

Pachyonychia Congenita — Know It All!

Editorial

Pachyonychia Congenita — Know It All!

All you need to know about Pachyonychia Congenita.

Pachyonychia Congenita 

Know your ailment well, so you can manage it better!!

Here we come with Jackson-Lawler syndrome today!

Overview:

Pachyonychia Congenita is also known as:

  • Congenital pachyonychia
  • Jackson-Lawler syndrome (PC-2)
  • Jadassohn-Lewandowski syndrome (PC-1)
  • Pachyonychia congenita syndrome

Pachyonychia congenita is a disease often affecting the skin and nails. Typically within the first few years of life, the signs and symptoms of this disorder become evident.

Almost everyone with pachyonychia congenita shows some signs of hypertrophic nail dystrophy which leads to thick and abnormally formed fingernails and toenails. Even most affected children develop very painful blisters and calluses on the feet’s sole and, less frequently, on the hand palms. This disorder is known as palmoplantar keratoderma. Serious blisters and calluses on the feet usually start developing first in childhood as they start walking first, which may make walking painful or impossible.

Pachyonychia congenita may have several additional characteristics which differ among the individuals affected. These characteristics include thick, white patches on the tongue and within the cheeks (oral leukokeratosis); bumps called follicular keratoses that form around the elbows , knees, and waistline hair follicles; kysts in the armpits, neck , back, or scalp; and excessive sweating on the palms and soles (palmoplantar hyperhidrosis). Some individuals affected often develop widespread cysts called steatocystomas, which are filled with an oily substance called sebum that typically lubricates the skin and hair. Some babies with pachyonychia congenita have prenatal or natal teeth present at birth or early infancy. In certain cases, pachyonychia congenita can affect the voice box (larynx), which may cause heaviness or problems with breathing.

Researchers used the genetic cause and pattern of signs and symptoms to classify pachyonychia congenita as one of two forms, PC-1 or PC-2, based on. However, as more affected individuals were identified, it became apparent that there was significant overlap between the characteristics of the two forms. Now researchers prefer a gene-altered classification of pachyonychia congenita.

Pachyonychia congenita causes overgrowth of the nails and thick, painful calluses on the bottoms of the feet.

Who gets the disease:

  • Frequency of occurrence:

Although the exact frequency of pachyonychia congenita is unknown, it appears to be rare. An estimated 5,000–10,000 cases have been reported worldwide.

  • Sex:

Pachyonychia congenita affects both sexes equally.

  • Age:

Patients with pachyonychia congenita often present at birth or soon after with the characteristic hypertrophic toenail dystrophy.

Pachyonychia congenita is known to be an autosomal dominant syndrome, meaning one copy of the altered gene is available in each cell to induce the disorder. An affected individual inherits the mutation from one infected parent in around 60 to 70 per cent of all cases. Thirty to 40 per cent of cases arise from a new (de novo) gene mutation that occurs during reproductive cell formation (eggs or sperm) or early embryonic development. These cases arise in individuals that have no family history of the condition.

Symptoms:

Most Common Symptoms:

  1. Thickened Nails (hypertrophic nail dystrophy or pachy-onychia) although not all nails are affected in all patients with PC.
  2. Painful calluses and blisters on the soles of the feet (focal plantar hyperkeratosis). Pain is one of the distinct characteristics of PC. Blisters are found under the callus in PC patients. Calluses may also form on the palms of the hands (palmar hyperkeratosis).
  3. Cysts of various types (including steatocystoma and pilosebaceous cysts). In some forms of PC, this is the most dominant, painful, and problematic characteristic.
  4. Follicular hyperkeratosis (FHK or bumps around hairs at friction sites such as waist, hips, knees, elbows). Most common in children and lessens after teenage years.
  5. Leukokeratosis of the oral mucosa (white film on tongue and inside cheeks). This is not painful, but is often misdiagnosed as thrush or as leukoplakia.
  6. Neurovascular Structures in Calluses (painful blood vessels or nerve endings). These can grow in the calluses and make trimming difficult and walking extra painful.
  7. Deep itch under, around, or in the calluses. Like the painful calluses, this deep itching can interfere with sleep and make the feet feel uncomfortable and irritable.
Pachyonychia Congenita 

Less common features:

  1. Sores at the corner of the mouth (angular cheilitis).
  2. Teeth at or before birth (natal or pre-natal teeth). This is found in one subset of PC.
  3. Laryngeal involvement with a white keratin film on the larynx. This results in a hoarse cry or a hoarse voice and is found in only a few patients.
  4. Intense pain on first bite (‘first bite syndrome’). The pain is near the jaw or ears and lasts 15–25 seconds when beginning to eat or swallow. This is more common in younger children and is often confused with ear problems.

Types:

There are five forms of pachyonychia congenita, which are based on the altered gene. Among these genes are: KRT6A, KRT6B, KRT6C, KRT16, and KRT17. In all types of the disease thickened nails and calluses occur. Symptom incidence is primarily dependent upon the underlying genetic mutation.

Pachyonychia Congenita 

Causes:

Mutations of several genes, including KRT6A, KRT6B, KRT6C, KRT16, and KRT17, can cause congenital pachyonychia. All these genes give instructions on how to make tough, fibrous proteins called keratins. These proteins form networks that provide the tissues that make up the skin, hair , and nails with strength and resiliency.

When mutations in the KRT6A gene cause pachyonychia congenita, this is known as PC-K6a. Similarly, mutations in the KRT6B gene cause PC-K6b, mutations in the KRT6C gene cause PC-K6c, mutations in the KRT16 gene cause PC-K16 and mutations in the KRT17 gene cause PC-K17.

Mutations in keratin genes change the keratin protein structure, which prevents these proteins from forming solid , stable cellular networks. Skin cells become vulnerable without this network and are easily destroyed, rendering the skin less resistant to friction and mild trauma. Even normal activities such as walking will cause skin cells to break down causing extreme, painful blisters and calluses to form. Deficient keratins also impair the development and function of cells in the hair follicles and nails, resulting in other pachyonychia congenita characteristics.

Pachyonychia Congenita 

Diagnosis:

Laboratory Studies:

In pachyonychia congenita, molecular DNA review shows missense mutations, deletion mutations, substitution mutations, and other mutations of the K6a, K6b, K16, and K17 keratin genes.

Oral leukokeratosis is to be distinguished from leukoplakia or cancer by either conducting an oral biopsy or identifying its presence in patients with other pachyonychia congenita symptoms. Nail clipping or scraping culture or microscopy can help to distinguish candidal or fungal onychomycosis from pachyonychia.

Histologic Findings:

Histological analysis of plantar hyperkeratotic plaques shows an acanthotic epidermis associated with parakeratosis and orthokeratosis, with rapid proliferation and differentiation of keratinocytes. We do not see cytological atypia. Immunostaining exhibits positive immunostaining of K14, as predicted in the basal cell layer along with K6, K16, K17. The staining of K6, K16, K17, and K14 occurs in the supra basal layers and K10 staining emerges.

Electron microscopy reveals thickened and clumped intermediate filaments on palmar or plantar plaques, as well as swollen keratohyalin granules. Thick masses of tonofilaments and large, irregular keratohyalin granules are present in the broadened granular layer. Dense masses of tonofilaments are located in the spinous layer at the periphery of the cells.

Pachyonychia Congenita 

Treatment Options:

As with other genodermatoses, pachyonychia congenita is not recommended for specific treatment or cure. Therapy is usually targeted at symptomatically enhancing the disease’s most humiliating symptoms, and is primarily focused on anecdotal observations due to the prevalence of pachyonychia congenita.

One of the most severe aspects of the disease is thought to be the palmoplantar keratoderma and its associated discomfort. Pressure, weight, and trauma are important cofactors in keratoderma growth, and attempts to redistribute and reduce it are essential. Specially made shoes, orthotic caps, insoles, and protective socks and gloves will accomplish this. For patients with extreme pain and fissure, it may be helpful or even appropriate to use an outpatient aid such as crutches or a wheelchair for pain relief and healing.

It may be beneficial to mechanically thin the keratotic nails and calluses with a variety of tools such as pumice blocks, emery boards, rasps, and papers. Some patients reported the successful use of electrical tools to minimise thickened nails, such as grinders, polishers, and sanders.

Medical Care:

Water, humectants (e.g., urea, propylene glycol), and subtle organic acids ( e.g., salicylic acid, alpha-hydroxy acid) can also be used to soften the nose and callus.

Hyperhidrosis treatment, a troublesome and common feature of pachyonychia congenita, appears to be effective in reducing blistering and pain, and was achieved with agents such as aluminium chloride or plantar botulinum toxin injections.

Pachyonychia congenita prescription therapy includes systemic retinoids such as isotretinoin, and etretinate. Retinoids can increase tenderness and blistering in reducing follicular keratoses and palmoplantar keratoderma. Adverse effects, such as teratogenicity, adverse mucocutaneous effects, liver toxicity, hyperlipidemia and skeletal defects also limit their use as long-term therapy.

Evidence suggests that therapy with rapamycin (or rapamycin analogues) may also be a feasible method of treatment. The proposed action mechanism is a selective inhibition of an inducible form of keratin (K6a) in the human keratinocytes. The US Food and Drug Administration (FDA ) has approved Sirolimus as an orphan drug for the treatment of pachyonychia congenita. TransDerm, Inc. (Santa Cruz, Calif) is the sponsor of the orphanage. In 2018 , two patients considered the compounded topical 1 percent sirolimus ointment to be a safe and effective plantar keratoderma therapy.

Based on in vitro evidence that simvastatin and a statin precursor, compactin, decrease KRT6A gene transcription, [30] statin therapy has been suggested as worth investigating; a 2018 case study of successful rosuvastatin treatment in a paediatric patient with KRT6A mutation suggests that it could be a promising alternative.

Surgical Care:

Typically, surgical treatment of pachyonychia congenita is most effective in treating cysts that are treated no differently from cysts that arise outside of pachyonychia congenita, with normal steps such as incision and drainage or excision.

Treatment of pachyonychia with the affected nails’ avulsion has not been shown to be successful since the nails re-growth occurs, often with worse dystrophy and distortion. Nail-matrix ablation has been incoherently successful. There have been records of improved function and appearance of the nails following matrix ablation in some patients but not in others.

Excision and grafting of plantar skin in pachyonychia congenita did not show promise, due to the reappearance of hyperkeratosis.

Medications:

Retinoids :

Retinoids are a family of drugs related to vitamin A. They regulate the differentiation and proliferation of epithelial cells. Some also possess antitumor activity.

  • Acitretin

Retinoic acid analogues such as acitretin and isotretinoin are relatively widely used in dermatology. Etretinate is the main metabolite. The detailed mechanisms of action are still being studied.

Keratolytics

These agents cause cornified epithelium to swell, soften, macerate, and then desquamate.

  • Salicylic acid topical

By dissolving the intercellular cement substance, salicylic acid produces desquamation of the horny layer of skin, while not affecting structure of viable epidermis.

Hydrate skin and enhance the effects of the medication by soaking the affected area in warm water for 5 minutes prior to use. Remove any loose tissue with a brush, washcloth, or emery board and dry thoroughly. Improvement should generally occur in 1–2 weeks.

  • Urea

Urea promotes hydration and removal of excess keratin in conditions of hyperkeratosis.

  • Salicylic acid (20%), urea (40%), and hydrophilic ointment compound

This is compounded in the pharmacy. It promotes hydration and removal of excess keratin in conditions of hyperkeratosis.

Coping with PC:

There are no pachyonychia congenita drugs but there are things that you can do to deal with the condition. Including:

  • Nails and skin thickened to grin or shave away. Take care not to make them too thin, as this may cause discomfort and infection.
  • Wearing gloves during tasks such as riding a bicycle or using hand tools to cover the hands.
  • Wearing comfortable shoes and socks which reduce humidity. This decreases rubbing, which can make sore calluses worse.

 

References:

https://www.niams.nih.gov/health-topics/pachyonychia-congenita/advanced#tab-living-with

What Is Pachyonychia Congenita?

https://emedicine.medscape.com/article/1106169-medication#showall

https://ghr.nlm.nih.gov/condition/pachyonychia-congenita#synonyms

 

By,

Gopala Krishna Varshith,

Content Developer & Editor,

Clipo.

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