Onycholysis

Practice Essentials

Onycholysis is characterized by a spontaneous separation of the nail plate starting at the distal free margin and progressing proximally. (See the images below.) In onycholysis, the nail plate is separated from the underlying and/or lateral supporting structures. Less often, separation of the nail plate begins at the proximal nail and extends to the free edge, which is seen most often in psoriasis of the nails (termed onychomadesis). Rare cases of onycholysis are confined to the nail's lateral borders.

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Thumb onycholysis. Courtesy of DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/hair-nails-sweat/olysis1.jpg).

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Great toe onycholysis. Courtesy of Professor Raimo Suhonen and DermNet New Zealand (http://www.dermnetnz.org/assets/Uploads/hair-nails-sweat/s/olysis7....

Signs and symptoms

Nails are smooth, firm, and without inflammatory reaction.

Discoloration under the nail may occur as a result of secondary infection.

See Presentation for more detail.

Diagnosis

Laboratory studies may include the following:

• Mycologic studies to exclude onychomycosis
• Nail biopsy if mycologic studies do not yield a positive result

See Workup for more detail.

Management

Treatments may include topical or intralesional corticosteroids, pulsed-dye laser, or psoralen plus ultraviolet A (PUVA) light.

Severe cases of onycholysis that are left untreated may result in nail bed scarring.

See Treatment and Medication for more detail.

• References

Pathophysiology

Nails with onycholysis usually are smooth, firm, and without inflammatory reaction. Onycholysis is not a disease of the nail matrix, but nail discoloration may appear underneath the nail as a result of secondary infection. When onycholysis occurs, a coexistent yeast infection is suggested. Treating primary and secondary factors that exacerbate onycholysis is important. Left untreated, severe cases of onycholysis may result in nail bed scarring.

• References

Etiology of Onycholysis

Endogenous, exogenous, hereditary, and idiopathic factors can cause onycholysis. Contact irritants, trauma, and moisture are the most common causes of onycholysis, but other associations exist.

Endogenous factors in onycholysis

Systemic diseases and states in onycholysis are as follows:

• Amyloid and multiple myeloma
• Anemia (iron deficient)
• Bronchiectasis
• Diabetes mellitus
• Erythropoietic porphyria
• Histiocytosis X
• Hyperthyroidism^[1]
• Hypothyroidism
• Ischemia (peripheral, impaired circulation)
• Leprosy
• Lupus erythematosus
• Neuritis
• Pellagra
• Pemphigus vulgaris
• Pleural effusion
• Porphyria cutanea tarda
• Pregnancy
• Psoriatic arthritis^[2]
• Reiter syndrome
• Sarcoidosis
• Scleroderma
• Shell nail syndrome
• Syphilis
• Yellow nail syndrome

Dermatologic diseases in onycholysis are as follows:

• Psoriasis
• Lichen planus
• Dermatitis
• Hyperhidrosis
• Pachonychia congenita
• Congenital ectodermal defect
• Pemphigus vegetans
• Lichen striatus
• Atopic dermatitis
• Congenital abnormalities of the nail
• Neoplastic disorders in onycholysis are as follows:
• Squamous cell carcinoma (of nail bed)
• Carcinoma (lung)

Exogenous factors in onycholysis

Nonmicrobial factors in onycholysis (may be encountered at the job site, ie, as occupational onycholysis) are as follows:

• Mechanical - Mechanical force (trauma), repetitive minor trauma, or maceration
• Chemical - Allergic or irritant contact dermatitis from various nail cosmetics (methyl methacrylate monomer, formaldehyde 1-2%, nail base coat/hardeners, polymerized 2-ethylcyanoacrylate adhesive used in artificial nails, nail lacquer),^[3] gasoline, paint removers, dicyanodiamide, thioglycolate, solvents, and hydroxylamine sulphate in color developer
• Chemical - Irritant contact dermatitis from prolonged immersion of nails in water, sugar onycholysis in confectioners/bakers, and exposure to highly destructive toxins (eg, hydrofluoric acid)

Biologic/microbial factors are as follows:

• Dermatophytosis (ie, Trichophyton rubrum, Trichophyton mentagrophytes infection)
• Yeast (Candida infection)
• Bacteria (Pseudomonas infection^[4] )
• Virus (herpes simplex infection)

Drug associations with onycholysis

Photo-induced associations, with medication and subsequent exposure to sunlight, are as follows:

• Tetracycline and its derivatives
• Psoralens
• Fluoroquinolones
• Chloramphenicol
• Benoxaprofen
• Chlorpromazine
• Chlortetracycline
• Demethylchlortetracycline
• Doxycycline^{[5, 6]}
• Minocycline^[7]
• Oral contraceptives
• 5-Methoxypsoralen (Psoraderm 5)
• Aminolevulinic acid (from phototherapy)^[8]
• Olanzapine^[9]
• Aripiprazole^[9]
• Griseofulvin^[10]

Photo-induced associations with onycholysis, without medication and exposure to sunlight, are as follows:

• Spontaneous photo-onycholysis^[11]
• Bullous photo-onycholysis (during pseudoporphyria resulting from hemodialysis)
• Non–photo-induced associations with onycholysis^[12] are as follows:
• Doxorubicin
• Mitoxantrone
• Captopril
• Bleomycin
• 5-Fluorouracil (capecitabine)^{[13, 14]}
• Retinoids
• Tetracycline
• Etoposide
• Paclitaxel^{[15, 16]}
• Docetaxel^{[15, 17]}
• Hydroxylamine

Other factors in onycholysis

These include the following:

• Congenital onycholysis
• Hereditary partial onycholysis
• Idiopathic acquired onycholysis
• Hereditary distal onycholysis^[18]
• Foreign body implantation

• References

Epidemiology

The worldwide incidence of onycholysis is unknown.

Race-, sex-, and age-related demographics

Distribution of onycholysis by race is unknown; however, onycholysis has been observed in persons of all races.

Individuals of either sex can have onycholysis; however, studies demonstrate an overwhelmingly female predilection.

People of any age can present with onycholysis, although it primarily is a disease of adulthood.

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Patient Education

Educate patients with onycholysis about avoiding possible contact irritants, trauma, and moisture.

In addition, recommend that patients take the following measures:

• Keep nail beds dry
• Keep nails short; clip affected portions
• Wear light cotton gloves under vinyl gloves for wet work

For patient education resources, see the Skin Conditions & Beauty Center and the patient education articles Nail Psoriasis and Onychomycosis.

• References

History and Physical Examination

History

Evaluation of patients with onycholysis requires a careful history of exposure to etiologic agents.

Physical examination

In onycholysis, nails are smooth, firm, and without inflammatory reaction.

Discoloration underneath the nail may occur as a result of secondary infection.

Spontaneous separation of the nail plate in onycholysis starts at the distal free margin and progresses proximally. Less often, nail plate separation may begin at the proximal nail and extend to the free edge. The nail plate is separated from underlying and/or lateral supporting structures.

Nail plate separation can be confined to the nail's lateral borders (rare).

• References

Laboratory Studies

Perform mycologic studies to exclude onychomycosis, including potassium hydroxide wet mount and fungal cultures. If these studies do not yield a positive result, a nail biopsy and staining of the specimen with hematoxylin and eosin stain and periodic acid-Schiff (PAS) stain (for fungus) may be performed.

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Histologic Findings

Onycholysis is a clinical diagnosis and has no specific histology; however, if onychomycosis is the etiology for the onycholysis, hyphae are seen lying between the laminae of nail parallel to the surface. The ventral nail and the stratum corneum of the nail bed are affected preferentially. The epidermis may show spongiosis and focal parakeratosis. The inflammatory response in the dermis is minimal. Hyphae may be seen best using PAS stain.

• References

Medical Care

Treatment for onycholysis varies and depends on its cause. Eliminating the predisposing cause of the onycholysis is the best treatment.  Note the following:

• Patients should avoid trauma to the affected nail, and keep the nail bed dry.
• Patients should avoid exposure to contact irritants and moisture (important).
• Patients should clip the affected portion of the nail, and keep the nails short.
• Patients should wear light cotton gloves under vinyl gloves for wet work.

Onycholysis related to psoriasis or eczema may respond to a midstrength topical corticosteroid.  Psoralen plus ultraviolet A (PUVA) treatment has also been reported as an effective therapy for psoriatic onycholysis.^[19]   

Laser treatments, often in conjunction with topical agents, have shown favorable results in the treatment of nail psoriasis. A systematic review of 19 studies of pulse dye laser (PDL), long-pulsed neodymium:yttrium aluminum garnet (Nd:YAG) laser, and fractional carbon dioxide laser (FCL) inteventions reported all were effective in lowering Nail Psoriasis Severity Index (NAPSI) scores. In addition, PDL and Nd:YAG laser treatment were more effective at reducing nail bed features, while FCL was effective at reducing both nail bed and matrix features.^[20]

El-Basiony and colleagues used high-frequency ultrasound to assess the efficacy of ND:YAG laser treatment. Improvements in nail psoriasis were attributed to improved penetrability of topical agents into the nail bed and/or matrix following laser treatment.^[21]

Intralesional injection may be required for onycholysis associated with more severe psoriatic nail dystrophy. Note the following:

• Triamcinolone 2.5-5 mg/mL diluted with normal saline is injected into the proximal nail fold every 4 weeks in a series of 4-6 sessions.
• The proximal nail fold overlying the nail matrix is the ideal site for treatment of diseases that begin at the matrix (eg, psoriasis).
• A 30-gauge needle is adequate for medication delivery; a topical anesthetic may be used to reduce pain.
• Improvement should start after the initial series; continued injections depend on disease recurrence.
• For other nail changes associated with onycholysis (eg, oil drop sign of psoriasis, distal onycholysis, subungual hyperkeratosis), the ideal location for intralesional injection is the nail bed. The pain of this procedure necessitates the use of anesthesia. This problem can be overcome by injecting the lateral nail folds in an attempt to get medication to the affected area.

In a small series of 14 patients with onychodystrophy due to lichen planus, combination therapy with intramatricial triamcinolone and platelet-rich plasma (PRP) showed significant improvements in grades of dystrophy according to the Nail Dystrophy Grading System (NDGS), compared to treatment with intramatricial triamcinolone alone.^[22]

Several case reports and case series have described successful treatment of nail lichen planus with Janus kinase (JAK) inhibitors including upadacitinib, tofacitinib, baricitinib, and ruxolitinib.^{[23, 24]}

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Prevention

Patients with onycholysis should avoid contact irritants, trauma, and moisture.

Advise patients to take the following measures:

• Keep nail beds dry
• Keep nails short; clip affected portions
• Wear light cotton gloves under vinyl gloves for wet work

Docetaxel-induced onycholysis may be prevented by wearing a frozen glove for 90 minutes during infusion of the chemotherapeutic agent.^{[25, 26]}

• References

Medication Summary

In onycholysis, apply a topical antifungal imidazole or allylamine twice daily to avoid superinfection of the nail. An oral broad-spectrum antifungal agent (ie, fluconazole, itraconazole, terbinafine) may be used for cases with concomitant onychomycosis.

Midstrength topical corticosteroids are suitable for isolated onycholysis. High-potency topical steroids (eg, clobetasol ointment) under occlusion have been used with less than ideal results for patients with severe nail dystrophy unwilling to undergo intralesional injection of corticosteroids. Patients follow this regimen for 2 weeks and then discontinue use of topical steroids for 2 weeks to avoid the other local adverse effects of topical steroids.

Massaging 5-fluorouracil 1% solution twice a day into the proximal nail fold for 4 months has been effective for patients with nail pitting and hyperkeratosis from psoriasis. Application to the free end of the nail should be avoided, as this will cause onycholysis. Localized PUVA, oral etretinate, hydroxyurea, and isotretinoin are other agents that have had some success in treating onycholysis resulting from psoriasis.

Treatment is not without adverse effects. They may include subungual hematoma secondary to intralesional steroid injections and photo hemolysis secondary to PUVA treatment. Explain risks to patients before initiating therapy.

• References

Clotrimazole (Mycelex, Lotrimin)

• Dosing, Interactions, etc.

Clinical Context:  Clotrimazole is a broad-spectrum antifungal agent that inhibits yeast growth by altering cell membrane permeability, causing the death of fungal cells.

• References

Econazole topical (Ecoza)

• Dosing, Interactions, etc.

Clinical Context:  Econazole is effective in cutaneous infections. It interferes with RNA and protein synthesis and metabolism. Econazole disrupts fungal cell wall membrane permeability, causing fungal cell death.

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Ketoconazole topical (Nizoral)

• Dosing, Interactions, etc.

Clinical Context:  Ketoconazole is an imidazole broad-spectrum antifungal agent; it inhibits the synthesis of ergosterol, causing cellular components to leak, resulting in fungal cell death.

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Fluconazole (Diflucan)

• Dosing, Interactions, etc.

Clinical Context:  Fluconazole is a synthetic oral antifungal (broad-spectrum bistriazole) that selectively inhibits fungal cytochrome P450 and sterol C-14 alpha-demethylation.

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Itraconazole (Sporanox)

• Dosing, Interactions, etc.

Clinical Context:  Itraconazole has fungistatic activity. It is a synthetic triazole antifungal agent that slows fungal cell growth by inhibiting cytochrome P-450-dependent synthesis of ergosterol, a vital component of fungal cell membranes.

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Terbinafine (Lamisil)

• Dosing, Interactions, etc.

Clinical Context:  Terbinafine was the first oral allylamine antimycotic agent to be released, having a different mode of action than the azoles. It is considered to be fungicidal, rather than fungistatic. It inhibits the enzyme squalene epoxidase in the sterol synthesis pathway.

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Class Summary

Antifungals treat superinfection of the onycholytic nail by dermatophytic molds and/or candidal yeasts.

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Triamcinolone (Aristocort)

• Dosing, Interactions, etc.

Clinical Context:  Triamcinolone is used for inflammatory dermatosis responsive to steroids. It decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing capillary permeability.

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Clobetasol (Temovate)

• Dosing, Interactions, etc.

Clinical Context:  Clobetasol is a class I superpotent topical steroid; it suppresses mitosis and increases synthesis of proteins that decrease inflammation and cause vasoconstriction.

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Class Summary

Corticosteroids treat noninfectious causes of onycholysis. They have anti-inflammatory properties and cause profound and varied metabolic effects. Corticosteroids modify the body's immune response to diverse stimuli. Intralesional and topical corticosteroids are designed to treat any noninfectious inflammatory condition associated with onycholysis with minimal risk for systemic absorption.

• References

Fluorouracil topical (Fluoroplex)

• Dosing, Interactions, etc.

Clinical Context:  Fluorouracil is a fluorinated pyrimidine analog used in topical form to treat actinic keratoses. It has an unknown mechanism in treating onycholysis. Use 1% solution.

• References

Class Summary

Topical pyrimidine antagonists inhibit cell growth and proliferation. Their mechanism is unknown for treating onycholysis. They are reported to be effective in the treatment of nail pitting and onycholysis associated with psoriasis.

• References