Periungual and subungual warts are usually difficult to treat and frequently recur. The
life span of periungual warts may be such that they—and the various treatments—may
exceed the patience of both patient and physician! Under such circumstances intelligent
placebo therapy may well be appropriate. A great variety of treatments are listed in all
pharmacopoeias, reflecting their individually limited success rates. The choice of
treatment depends on:
• number of warts
• location (periungual and subungual)
• duration
• age of the patient
• immunological status
• skills of the doctor.
Surgical procedures should be restricted to selected cases.

Topical treatment
Topical agents include: keratolytic agents, virucidal agents and immunomodulators.

Keratolytic agents
Keratolytic agents are the most popular first-line treatment of warts and are particularly
suitable for young children, who can apply at home creams, ointments, tapes or quick-
drying acrylate lacquers containing salicylic acid in concentrations ranging from 10% to
40%.

Virucidal agents
Both glutaraldehyde and formaldehyde combine with keratin and produce skin
desiccation with viral destruction. Effectiveness is comparable to that of keratolytic
agents.

Immunotherapy
Topical immunotherapy with strong topical sensitizers—squaric acid dibutylester
(SADBE) or diphenylcyclopropenone (DPCP)—is an effective and painless treatment for
multiple warts. A preparation of SADBE or DPCP 2% in acetone is used for
sensitization. After 21 days weekly applications are carried out with dilutions ranging
from 0.001% to 1% according to the patient’s response. The objective of treatment is to
induce a mild contact dermatitis.
Imiquimod acts as an immunomodulator owing to its capacity to induce cytokine
(especially interferon alpha) production. Although imiquimod has only been used for
treatment of genital and facial warts, its effectiveness in these regions suggests its
possible use for periungual warts.

Systemic treatment

Oral immunomodulators 
The efficacy of cimetidine 750–1200 mg per day has never been definitively proved. The
drug is expensive and not always well tolerated.

Interferon
The efficacy of interferons is still debated and the necessity of intravenous administration
together with cost of treatment do not recommend its routine use. However, complete
cure of recalcitrant and extensive periungual and subungual warts has been reported after
interferon beta treatment.

Antimitotics 
Intralesional injections of bleomycin are effective in the treatment of periungual warts.
After local anaesthesia, the bleomycin solution (1 U bleomycin per 1 ml sterile saline) is
dropped on the wart surface. The wart is then punctured using a disposable needle
approximately 40 times per 5 mm2area. The wart slowly undergoes necrosis with
formation of an eschar that can be scraped away 3–4 weeks after treatment. Residual
warts can be retreated.

Surgical treatment

Cryotherapy 
Freezing warts with liquid nitrogen is a rapid method of treatment. It is contraindicated
in small children, since it is frequently associated with intense pain secondary to oedema
under the nail bed. Application of a surface anaesthetic cream 1–2 hours prior to therapy
does not help to reduce pain in the periungual region. Hyperkeratotic warts should be
pared off before treatment to permit freezing of the deeper portions of the wart. Freezing
takes 10–15 seconds using cryogen spray. A 1 mm halo ring should form in the normal
skin surrounding the wart. Cryosurgery should be used with caution for warts on the
proximal nail fold, since nail matrix damage is a common complication, with
leukonychia, Beau’s lines and onychomadesis. Irreversible matrix destruction with nail
atrophy has been reported after overzealous cryosurgery.

Surgical excision 
Excision of periungual warts is not recommended since it produces scarring and is
associated with a high frequency of recurrence.
•   Electrosurgery should be avoided, since it produces considerable scarring.
•   Infrared coagulation is another destructive method that is not recommended.
•   Localized heating using a radiofrequency heat generator has been successfully used
to treat hand warts (86% cure). This treatment is not particularly painful, but may
cause scarring and does not seem suitable for periungual warts.

Laser techniques 
•   Carbon dioxide laser: this causes thermic destruction of the wart, producing a loss
of skin which heals by secondary intention. When warts extend into the nail folds or
the nail bed, laser treatment should be preceded by partial or total nail avulsion. Re-
epithelialization takes a long time (approximately 9 weeks) and is associated with
risk of infections and pain. Some authors reported complete cures in 71% of
patients with periungual warts exclusively treated with one or two sessions of CO2
laser. Temporary or permanent nail dystrophy were observed in 29% of treated
patients. Pain sometimes persists after wound healing. Scarring is not rare, as well
as disturbance of function. This technique is suggested only as a secondary
approach for recalcitrant warts.
•   Pulsed dye laser: this laser acts through a selective microvascular destruction of the
dilated capillaries of the warts, since the oxyhaemoglobin contained in the vessels
preferentially absorbs yellow light. Healing of the wart is due both to thermic
damage and to removal of the blood supply. Stimulation of a cell-mediated immune
response may be another contributing factor. A few days after the procedure the
wart becomes dry and black, as a result of necrosis. Since no wound is produced,
patients may return to work immediately and postoperative pain is minimal. Healing
occurs after 2–4 weeks. Periungual warts are less responsive to treatment than
palmar or common warts. Although this technique is associated with a very low
incidence of scarring, cure is achieved in only a third of cases, and usually after two
to four treatments.
•   Erbium:YAG laser: the erbium:ytrium-aluminium-garnet (YAG) laser produces a
controlled tissue ablation with minimal thermal damage compared with the CO2
laser. This laser has been used for periungual warts with an excellent safety profile
and minimal morbidity and pain.

Frequent application of distasteful topical preparations on the nail and periungual skin
can discourage patients from biting and chewing their finger nails. Possible alternatives
include:
•   1% clindamycin
•   quaternary ammonium derivatives
•   4% quinine sulphate in petrolatum.
Patients with severe onychophagia or median nail dystrophy can be helped by daily
bandaging the injured fingers with permeable adhesive tape. Fluoxetine at high dosages
(60 mg/day) can be helpful in interrupting this compulsive disorder in adults.

Yellow nail syndrome is an uncommon disorder of unknown aetiology, characterized by
the triad of yellow nails, lymphoedema and respiratory tract involvement. Vitamin E at
dosages ranging from 600 to 1200 IU daily can induce a complete clearing of the nail
changes. Although the mechanism of action of vitamin E in yellow nail syndrome is still
unknown, antioxidant properties of alpha-tocopherol may account for its efficacy. A 5%
solution of vitamin E in dimethyl sulphoxide produced marked clinical improvement in a
double-blind controlled study. The efficacy of topical vitamin E, however, still needs
confirmation. Oral itraconazole, 400 mg daily one week a month for several months, or
oral flucouazole, may be beneficial in some cases.

Twenty-nail dystrophy, characterized by nail roughness, can be idiopathic or associated
with alopecia areata and less often with lichen planus. It is a benign condition that never
causes nail scarring. The nail changes usually regress spontaneously in a few years.
Reassuring the patient is probably the best approach to this nail disorder. Although
topical PUVA can be effective, continuous treatment is required to maintain the results.

Specific nail involvement occurs in about 10% of patients with lichen planus and
permanent damage of at least one nail occurs in approximately 4% of patients. However,
if lichen planus is correctly diagnosed and treated, permanent damage to the nail unit is
rare, even where there is diffuse involvement of the nail matrix.
Systemic steroids are effective in treating nail lichen planus: intramuscular
triamcinolone acetonide 0.5 mg/kg every month for 2–3 months usually produces
recovery of the nail abnormalities. Intralesional injections of triamcinolone acetonide
10mg/ml represent a possible, but painful, alternative when the disease is limited to a few
finger nails. Mild relapses are frequently observed, but recurrences are usually
responsive to therapy. Steroid treatment is not useful in pterygium, since the nail matrix
cannot be regenerated. Systemic retinoids at dosages suitable for psoriasis are a good
alternative.

Since treatment of nail psoriasis is always disappointing, before treatment is started the
individual problems of every patient should be carefully considered, and in particular the
degree of discomfort that results from the nail lesions. Reassuring the patient is probably
the best approach for isolated nail pitting, oily patches, mild onycholysis and splinter
haemorrhages. However, diffuse onycholysis, subungual hyperkeratosis and severe nail
plate surface abnormalities may require a positive therapeutic approach.

Local therapies of nail psoriasis only rarely induce complete
remission of the disease

When the nail folds are affected, regular application of topical emollients is useful to
reduce scaling and prevent self-induced trauma.
Topical steroids, or combinations of topical steroids with salicylic acid and/or retinoic
acid, are widely prescribed. Their efficacy is poor, even when applied with occlusive
dressing after chemical or mechanical avulsion of the onycholytic nail plate. Long-term
application of topical steroids may result in marked atrophy of the soft tissues of the
digits or even in focal resorption of the distal phalanges.
A nail lacquer containing 8% clobetasol propionate, formulated to optimize
penetration of the drug through the nail plate, has been developed for use in this
condition. This topical treatment, which is effective and well tolerated, produces
improvement in most cases of nail psoriasis, with effects directly related to the duration
of treatment.
Topical calcipotriol is effective when onycholysis and subungual hyperkeratosis are
prominent symptoms. Topical tazarotene 0.1 % gel has also been used with good results
and tolerability in psoriasis. The latter drug is especially effective in reducing
onycholysis (in occluded and non-occluded nails) and pitting (in occluded nails).
Topical psoralens followed by exposure to ultraviolet-A (PUVA) are not very effective
owing to poor penetration of the UVA through the nail plate, especially when the plate is
thickened. However, this treatment may be useful in pustular psoriasis when recurrent
pustular lesions have destroyed the nail plate. Intralesional injections of triamcinolone
acetonide 10 mg/ml, at a dose of 0.2–0.5 ml per nail, have proved effective in some cases
of nail matrix psoriasis. In patients with nail-plate surface abnormalities the steroids
should be injected in the nail matrix, whereas in patients with subungual hyperkeratosis
the site of injection should be the nail bed. Injections should be repeated monthly for 6
months, then every 6 weeks for the next 6 months and finally every 2 months for 6–12
months. A digital block is sometimes useful to make the treatment less painful, but when
several digits are involved, a wrist block may be the appropriate anaesthesia. However,
routine use of this treatment is not recommended because of the pain caused by the
injections, the local side-effects and recurrence of the nail abnormalities after
discontinuation of the therapy. In addition, the efficacy of intralesional steroids in nail
matrix psoriasis is limited, with only 50% success in treating nail pits.
Systemic treatment with methotrexate or cyclosporin can clear the nail changes, but
this can be recommended only when nail psoriasis is associated with widespread disease
or psoriatic arthritis.
Retinoids are of little value in the treatment of nail psoriasis except for hyperkeratotic
nails and pustular psoriasis. Oral administration of etretinate or acitretin can even worsen
the nail changes owing to the development of nail brittleness, pyogenic granuloma-like
lesions and chronic paronychia. Oral photochemotherapy can improve crumbling of the
nail plate and psoriatic involvement of the proximal nail fold, but is less effective in nail
pitting or subungual hyperkeratosis. Superficial radiotherapy can have a beneficial effect
on psoriatic nails but is not recommended because the benefits are short-lived.
Pustular psoriasis of the nail unit usually fails to respond to conventional topical
treatments. Local treatment with topical anti-metabolites (mechlorethamine, 1 %
fluorouracil) is an option, even though results are variable. Systemic steroids, PUVA and
cyclosporin can arrest the development of pustular lesions and avoid permanent scarring
of the nail apparatus. A study of 46 patients with pustular psoriasis of the nails indicates
that systemic retinoids at low dosage (less than 0.5 mg of acitretin per day) are the
treatment of choice in patients with multiple nail involvement, whereas topical
calcipotriol is the best option for pustular psoriasis limited to one or two nails. Topical
calcipotriol is also useful as maintenance therapy in patients who responded to retinoids,
in order to prevent recurrence.

Onycholysis (detachment of the nail plate from the nail bed) starts in the central or lateral
portion of the nail plate free margin, progresses proximally and can even involve the
whole nail. The onycholytic area looks whitish because of the presence of air under the
detached nail plate. It may occasionally show a greenish or brown discoloration due to
colonization of the onycholytic space by chromogenic bacteria    (Pseudomonas
aeruginosa), moulds or yeasts. Onycholysis may be idiopathic or represent a symptom of
numerous diseases (such as psoriasis, onychomycosis or contact dermatitis) or drug
reactions.
Depending on the cause of the complaint (e.g. disease or impaired peripheral
circulation), appropriate local treatment, systemic treatment or both is prescribed. The
detached nail should be clipped away and a mild antibacterial solution (thymol 4% in
chloroform) should be applied on the exposed nail bed at night. Pseudomonas infection
is easily treated by using sodium hypochlorite solution or 2% acetic acid. Accurate
drying of the fingers after hand washing is necessary. A hair dryer may be useful for this
purpose.

Chronic paronychia represents an inflammatory reaction of the proximal nail fold to
irritants or allergens. It affects hands that are continually exposed to a wet environment
and to multiple microtrauma, favouring cuticle damage. Secondary colonization with
Candida albicans and/or bacteria occurs in most cases.
Patients with chronic paronychia should avoid a wet environment, chronic
microtrauma and contact with irritants or allergens. Application of high-potency topical
steroids (clobetasol propionate 0.05%) once a day at bedtime is an effective first-line
therapy. If    Candida is present a topical imidazole derivative should be applied in the
morning. Topical antifungal agents alone and systemic antifungal therapy are not useful.
In severe cases, intralesional or even systemic steroids (prednisone 20 mg/day) can be
used for a few days to obtain a prompt reduction of inflammation and pain. Acute
exacerbations of chronic paronychia do not necessitate antibiotic treatment since they
subside spontaneously in a short time. Pseudomonas colonization can be treated with
sodium hypochlorite solution or 2% acetic acid. Complete recovery of the condition
usually requires several weeks and treatment should be continued until the cuticle has
regrown. Recurrences are frequent since the barrier function of the proximal nail fold
may be impaired for months or even years after an episode of chronic paronychia. In rare
cases, foreign bodies such as hair or fibreglass spicules can be responsible for chronic
paronychia. These patients should be treated by the excision of a crescent-shaped, full-
thickness piece of the proximal nail fold, including its swollen portion. Complete healing
by granulation takes about 4 weeks.

Blistering distal dactylitis is a childhood disease usually caused by    ? hemolytic
streptococcus infection, characterized by bullous lesions with purulent content localized
at the tip of the digits. Treatment includes surgical drainage of the blisters, topical
medication with antiseptics and systemic antibiotics (oral erythromycin or amoxicillin).

Chemical avulsion of the overgrowing nail plate with urea ointment is useful and
provides considerable relief of the patient’s discomfort. Different formulations can be
used, ranging from a simple 40% urea in 60% white petrolatum preparation, to the South
and Farber’s ointment, which has the following formulation: urea 40%, white beeswax
5%, anhydrous lanolin 20%, white petrolatum 25%, micronized silica gel 10%. Before
the ointment is applied to the nail plate surface, it is mandatory to cover the periungual
skin with plastic tape in order to protect the skin from maceration. The urea ointment is
then applied to the nail and covered with a plastic wrap; the medication is fixed to the
digit with a plastic tape and maintained in place for 7–10 days. Finally, the medication is
wiped off and the softened nail plate is removed using nail clippers.
Chemical nail avulsion is only effective when the nail plate is partially or totally
detached from the nail bed. It is not useful on normal nails, but can be successful in
removing onychomycotic nails as well as thickened psoriatic nails.