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Home , Onycholysis, Onychomycosis, Paronychia, Thymol

REVIEW

Treatment of disorders

Bianca Maria Piraccini, There are several reasons that make the nail unit difficult to treat. It is necessary to wait for Matilde Iorizzo, several months before seeing the results of treatments in nail disorders, as the nail plate Angela Antonucci and Antonella Tosti† grows very slowly (average nail growth is 3 mm/month in fingernails and 1–1.5 mm/month in toenails). It is very important to give the patients this information, as they may otherwise †Author for correspondence Department of , discontinue the treatment feeling it to be ineffective. Delivery of topical drugs through the University of Bologna, nail is difficult, as vehicles utilized for enhancing penetration of drugs through the skin are Via Massarenti 1 – 40138 not effective in the nail. Most topical drugs are therefore ineffective in the treatment of Bologna, Italy Tel.: +39 051 341 820 inflammatory nail disorders, since the nails are largely exposed to environmental hazards and Fax: +39 051 347 847 nail disorders are commonly precipitated or worsened by physical traumas. Thus, clinicians [email protected] often do not prescribe systemic treatment when the disease is limited only to the nails.

Brittle nails Topical treatment Nail brittleness is a common complaint character- Nail moisturizers are useful. They may contain ized by weak nails that split, flake and crumble. It occlusives such as petrolatum or lanoline and may be a consequence of factors that alter the nail humectants, such as glycerin and propylenegly- plate production and/or factors that damage the col. Proteins, fluorides and silicium can also be already keratinized nail plate [1–3]. Since environ- useful. and α-hydroxy acids increase the mental and occupational factors that produce a water binding capacity of the nail plate [5]. progressive dehydration of the nail plate play a main role in the development of idiopathic nail Systemic treatment brittleness [4], the management of brittle nails • Biotin 2.5–5 mg/daily for 6 months [6] includes protective measures that prevent nail • Iron supplementation is useful ony when ferritin plate dehydration. Patients should be instructed levels are below 10 ng/ml to pursue the following rules: • Colloidal silicic acid has been reported effective • Avoid repeated immersion of the hands in at the dosage of 10 ml/day [7] soap and water • Avoid repeated use of nail polish removers that decrease nail content in water Onycholysis describes the detachment of the • Keep nails short and squared, and leave nail plate from the nail bed. It may be idio- cuticles uncut pathic, traumatic or may be a symptom of • Protect hands with rubber gloves worn over numerous diseases that affect the nail bed. The light cotton gloves during housekeeping onycholytic area appears whitish due to the presence of air under the detached nail plate. Cosmetic treatment It may occasionally present a green or brown Nail hardeners, nail strengtheners and fortify- discoloration due to colonization of the ony- ing nail builders are commercially available to cholytic space by chromogenic bacteria (Pseu- enhance the appearance of nails but there are domonas aeruginosa), or . A water- no data proving their efficacy. Nail varnishes borne environment facilitates the development may be useful to protect the nail plate from of this condition. Keywords: environmental hazards but they always need to drugs, nail diseases, therapy be removed with nail polish removers. For this Topical treatment reason, nail polishes should be applied once • The detached nail plate should be clipped a week. In recalcitrant fragility, nail wrapping away and this should be repeated at 2-week limited to the distal portion of the nail plate as intervals until the nail plate grows attached well as preformed artificial nails and sculptured • The exposed nail bed should be carefully dried Future Drugs Ltd nails may afford protection and camouflage [5]. after each hand washing

2004 © Future Drugs Ltd ISSN 1475-0708 http://www.future-drugs.com Therapy (2004) 1(1), 159–167 159 REVIEW – Piraccini, Iorizzo, Antonucci & Tosti

• Application of a topical solution Topical treatment (4% thymol in , or in 95% etha- Application of a mild potency topical at nol) and/or a topical on the night and a topical preparation containing a exposed nail bed may be useful steroid and an derivative in the morning. • Pseudomonas colonization can be treated with Systemic treatment sodium hypochlorite solution or 2% acetic • Systemic (methylprednisone acid 20 mg/day for a few days) can be prescribed • Treatment of the causative condition is in severe cases when several digits are affected required in all cases of onycholysis secondary • Systemic are often useless as to nail bed diseases chronic is not a mycotic Acute paronychia is a colonizer of the proximal nail fold Acute paronychia is an acute inflammatory dis- that disappears when the proximal nail fold bar- order affecting the proximal and lateral nail rier is restored. Eradication of Candida is not folds. It is usually caused by Staphylococcus associated with clinical cure [8]. aureus, although other bacteria and herpes sim- plex virus (HSV) 1 and 2 may be responsible for Surgical treatment this condition. The affected digit is painful, with Paronychia that is not responding to medical , swelling and discharge. Nonpuru- therapy should be treated by the excision of a cres- lent vescicles are typical of HSV infection. Treat- cent-shaped, full thickness piece of the proximal ment should commence as early as possible to nail fold, including its swollen portion. avoid deeper and progression to chronic paronychia with or without permanent nail plate damage. Onychomycosis is the most common nail dis- ease and describes the infection of the nail by Topical treatment fungi. Approximately 85% of cases of ony- Drainage of the and local chomycosis result from dermatophytic invasion with (4% thymol in chloroform or in of the nail. Nondermatophytic molds (NDM) 95% ethanol) are useful to obtain relief of account for 15% of cases, while onychomycosis and pain. due to yeasts are rare. Onychomycosis affects toenails more frequently Systemic treatment than fingernails. Different clinical patterns of Whenever possible, cultures should be taken. infection depend on the method by which fungal Treatment includes penicillase-resistant colonization of the nail occurs. Distal subungual or systemic acyclovir (Zovirax®, GlaxoSmithKline) onychomycosis (DSO), proximal subungual ony- in case of HSV infection. chomycosis (PSO), white superficial onychomyco- sis (WSO), endonyx onychomycosis (EO) and Chronic paronychia total dystrophyc onychomycosis (TDO) are the Chronic paronychia is a chronic inflammatory pattern currently described by the literature. reaction of the proximal nail fold due to irri- Treatment of onychomycosis depends on the tants or allergens. Secondary colonization with responsible fungi, the type of onychomycosis, and/or bacteria occurs in the number of affected nails and the patient’s age most cases, causing self-limited episodes of and general health. Since painful acute inflammation. of onychomycosis includes a large number of Clinically, the proximal and lateral nail folds different diseases, treatment should only be show mild erythema and swelling. The cuticle is commenced when the diagnosis is confirmed by generally lost. Beau’s lines (transverse superficial a positive microscopy and/or culture [9]. depressions of the nail plate) and onychomadesis (a transverse whole thickness sulcus that splits Onychomycosis due to the nail plate into two parts) may occur as a con- The affected digit demonstrates subungual hyperk- sequence of nail matrix damage. Management of eratosis with onycholysis in DSO; proximal leu- chronic paronychia requires avoidance of wet konychia in PSO; superficial friable in environment, chronic microtrauma and contact WSO. Onychomycosis due to dermatophytes are with irritants or allergens. most commonly due to rubrum.

160 Therapy (2004) 1(1) Treatment of nail disorders – REVIEW

Topical treatment • Recurrences and reinfections are not uncom- • In WSO colonization is limited mon (up to 20% of cured patients). Weekly to the most superficial layers of the nail plate. application of antifungal nail lacquers on the Treatment requires scraping of the affected previously affected nails and antifungal nail area followed by the application of a topical creams on the plantar and interdigital skin antifungal nail lacquer for 6–12 months can be performed to attempt to maintain ( [Loceryl®, ] 5% nail cures. lacquer 1–2 times/week or cyclopiroxolamine 8% nail lacquer once a day) • Sequential treatment with and ter- binafine has been utilized to increase cure rates • DSO usually requires systemic antifungals, how- [11]: the suggested regimen is two pulses of itra- ever, an exception may be represented by DSO conazole 400 mg per day for 1 week a month limited to the distal nail of a few digits. This can followed by one or two pulses of be treated with a nail lacquer as for WSO 500mg/day for 1week amonth.

Systemic treatment Onychomycosis due to NDMS Terbinafine (Lamisil®, Novartis Pharmaceuti- Although the list of NDM that have been isolated cals Corp.) and itraconazole (Sporanox®, Janss- from nails is relatively long, only a few species are sen-Cilag) have been demonstrated to reach the regularly identified as causing onychomycosis. distal nail soon after therapy is commenced and These include Scopulariopsis brevicaulis, to persist in the nail plate for a relatively long sp., Acremonium sp., sp., Scytalidium time (1 to 6 months) after interruption of sp. and Onychocola canadiensis.The presence of treatment. The persistence of high post-treat- periungual inflammation with or without puru- ment drug levels in the nail permits a short lent discharge usually strongly suggests a treatment period with fewer incidences of onychomycosis. relapses and side effects. Systemic treatment • Terbinafine is an allylamine derivative admin- istered at the dosage of 250 mg per day for Systemic treatment is scarcely useful for ony- 6 weeks (fingernail infections) to 3 months chomycosis due to Acremonium sp., Fusarium sp., (toenail infections). Terbinafine can also be S. brevicaulis and Scytalidium sp. Itraconazole and administered as pulse therapy at a dosage of terbinafine are effective in nail infections due to 500 mg daily for 1 week every month for 2 to Aspergillus sp. 4months [10]. Interactions with other drugs are extremely rare. Hepatobiliary diseases and Topical treatment white blood cell disturbances may occur Nail lacquers are quite effective in PSO or DSO rarely and patients should be assessed before due to S. brevicaulis, Fusarium sp. and Acremo- commencing treatment. nium sp. (Figure 1a & 1b). Chemical nail avulsion with 40% urea in white petrolatum greatly • Itraconazole is a triazole derivative adminis- increases the chance of cure. Scytalidium sp. tered as pulse therapy at a dosage of 400 mg infections are usually unresponsive to treatment. daily for 1 week every month. The duration of treatment ranges from 2 (fingernail infec- Candida onychomycosis tions) to 3–4 months (toenail infections). Onychomycosis due to C. albicans usually The drug should be administered with a high- indicates an underlying fat meal to improve its absorption. Due to its and the condition is almost exclusively seen in pharmacological interactions, it should be chronic mucocutaneous (CMCC), used cautiously in elderly patients who are in HIV-positive patients and patients undergo- taking multiple drugs. ing long-term steroid treatment. However, iso- • Patients treated with systemic antifungals lation of Candida in onychomycosis can be should be followed up for 4 to 12 months after occasionally observed in immunocompetent discontinuation of therapy to evaluate efficacy. individuals. Cure rates of onychomycosis with systemic antifungals are of 98% for fingernail infections Systemic treatment and 80% for toenail infections, with terbinafine • Itraconazole 200 mg per day and flucona- ® being the most effective treatment. zole (Diflucan , Pfizer) 150 mg weekly are www.future-drugs.com 161 REVIEW – Piraccini, Iorizzo, Antonucci & Tosti

Figure 1 (A–B). Distal sublungual onychomycosis.

AB

Figure 1 (A–B). Distal subungual onychomycosis due to Fusarium solani improved by 12 months of treatment with ciclopiroxolamine 8% nail lacquer.

effective. Duration of treatment is 6 weeks • cauterization: after removal of the for fingernails and 3 months for toenails lateral strip of the offending nail, hemostasis • Recurrences are common if the underlying is achieved with a tourniquet. Then, the sur- predisposing disease persists rounding skin is protected with petrolatum and a saturated solution of phenol 88% is Ingrown toenails rubbed to the lateral matrix horn on a small Ingrown toenails are a common complaint that cotton pack for 3 min, followed by neutrali- usually affect the big toe of young adults but zation with . The first dressing is per- they may occur at any age. They may be caused formed with an high potency by an incorrect nail trimming, traumas, podi- (clobetasol propionate 0.05% ointment) and atric abnormalities or . The con- changed after 24 h. The patient should be dition is due to a spicule that breaks off from instructed to soak the foot twice daily in a the lateral edge of the nail plate and penetrates quart of warm water containing three cap- into the tissues of the lateral nail fold. Con- sules of povidone-iodine. This accelerates servative treatment is indicated for early stages healing and prevents possible secondary but advanced disease often requires surgical infections [12]. treatment for definite cure. • Lateral matrix excision: this may be obtained Topical treatment by dissecting and excising the lateral matrix • Stage I: the embedded spicule must be removed horn [12]. and a package of nonabsorbent cotton soaked in a (povidone iodine) is placed Distal nail embedding under the lateral corner of the nail plate to sep- Distal nail embedding is a common complica- arate it from the distal and lateral nail folds. tion of total nail plate avulsion. An overgrowth This should be repeated daily. of distal soft tissue may occur and the new nail may penetrate into this, producing inflamma- • Stage II: high potency topical steroid (clobeta- tion with pain. Sculptured artificial nails may sol propionate 0.05% ointment [Temovate®, be useful to override the distal nail wall. GlaxoSmithKline]) should be applied for a few days to promptly reduce the overgrowth of Surgical treatment granulation tissue. Infection is always present In severe cases, a crescent wedge tissue excision is requiring application of topical mupirocin. performed around the entire distal phalanx.

Surgical treatment Congenital malalignment of the Stage III: selective destruction of the lateral big toenail horn of the nail matrix is mandatory and may Congenital malalignment of the big toenail is be achieved by phenol cauterization or by characterized by lateral deviation of the nail surgical lateral matrix excision [12]. plate with respect to the longitudinal axis of the

162 Therapy (2004) 1(1) Treatment of nail disorders – REVIEW

scanning electron microscopy. J. Am. 12 Haneke E. Nail surgery. Eur. J. Dermatol. 21 Tosti A, Piraccini BM, Iorizzo M. Acad. Dermatol. 23(6), 1127–1132 10(3), 237–241 (2000). Systemic itraconazole in the yellow nail (1990). •• Etiology and treatment of nail syndrome. Br. J. Dermatol. 146(6), 1064– 7 Lassus A. Colliodal silicic acid for oral and malalignment are well detailed by the 1067 (2002). topical treatment of aged skin, fragile authors. •• Review of of the nail unit and its and brittle nails in females. J. Int. Med. 13 Baran R, Haneke E. Etiology and treatment. Res. 21, 209–215 (1993). treatment of nail malalignment. Dermatol. 22 Tosti A, Piraccini BM. Warts of the nail 8 Tosti A, Piraccini BM, Ghetti E, Surg. 24(7), 719–721 (1998). unit: surgical and nonsurgical approaches. Colombo MD. Topical steroids versus 14 Cohen PR, Sher RK. Geriatric nail Dermatol. Surg. 27(3), 235–239 (2001). systemic antifungals in the treatment of disorders: diagnosis and treatment. J. Am. 23 Geyer AS, Onumah N, Uyttendaele H, chronic paronychia: an open, randomized Acad. Dermatol. 26(4), 521–531 (1992). Scher RK. Modulation of linear nail double-blind and double dummy study. J. 15 Baran R, Haneke E, Richert B. Pincer growth to treat diseases of the nail. J. Am. Am. Acad. Dermatol. 47(1), 73–76 nails. Definition and surgical treatment. Acad. Dermatol. 50(2), 229–234 (2004). (2002). Dermatol. Surg. 27(3), 261–266 (2001). • Demonstrates the effective role of Affiliations 16 Scher RK, Stiller M, Zhu YI. Tazarotene Candida in chronic paronychia. 0.1% gel in the treatment of fingernail • Bianca Maria Piraccini, MD, PhD 9 Tosti A, Piraccini BM, Lorenzi S, Iorizzo : a double-blind, randomized, Department of Dermatology, University M. Treatment of nondermatophyte mold vehicle-controlled study. Cutis 68(5), of Bologna Via Massarenti 1–40138 Bologna (Italy) and Candida onychomycosis. Dermatol. 355–358 (2001). Clin. 21(3), 491–497 (2003). Tel.: +39 051 341 820 17 Piraccini BM, Tosti A, Iorizzo M, Misciali •• A review of NDM and Candida Fax: +39 051 347 847 C. Pustular psoriasis of the nails: onychomycosis both in its clinical • Matilde Iorizzo, MD treatment and long-term follow-up of 46 presentations and treatments. Department of Dermatology, University patients. Br. J. Dermatol. 144(5), 1000– of Bologna Via Massarenti 1–40138 10 Tosti A, Piraccini BM, Stinchi C et al. 1005 (2001). Bologna (Italy) Treatment of dermatophyte nail Tel.: +39 051 341 820 18 Tosti A, Peluso AM, Zucchelli V. Clinical infections: an open randomized study features and long-term follow-up of 20 Fax: +39 051 347 847 comparing intermittent terbinafine • Angela Antonucci, MD cases of parakeratosis pustulosa. Pediatr. therapy with continuous terbinafine Department of Dermatology, University Dermatol. 15(4), 259–263 (1998). treatment and intermittent itraconazole of Bologna Via Massarenti 1–40138 therapy. J. Am. Acad. Dermatol. 34(4), 19 Tosti A, Peluso AM, Fanti PA, Piraccini Bologna (Italy) 595–600 (1996). BM. Nail : clinical and Tel.: +39 051 341 820 pathologic study of 24 patients. J. Am. Fax: +39 051 347 847 11 Gupta AK, Lynde CW, Konnikov N. Acad. Dermatol. 28(5), 724–730 (1993). • Antonella Tosti, MD Single-blind, randomized, prospective Department of Dermatology, University study of sequential itraconazole and 20 Tosti A, Piraccini BM, Iorizzo M. of Bologna Via Massarenti 1–40138 terbinafine pulse compared with Trachyonychia and related disorders: Bologna (Italy) evaluation and treatment plans. Dermatol. terbinafine pulse for the treatment of Tel.: +39 051 341 820 Ther. 15, 121–125 (2002). toenail onychomycosis. J. Am. Acad. Fax: +39 051 347 847 • Author's experience with the use of Dermatol. 44(3), 485–491 (2001). [email protected] itraconazole in the YNS.

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