Can Lamisil ruin your sense of smell

TREAT NAIL MYCOSIS:
LOCAL, SYSTEMIC - OR NOT AT ALL?

Onychomycosis is one of the most common nail diseases. Infections increase with age. Two to five percent of those over 35 are affected.1 A warm and humid environment promotes fungal attack on the skin. High infection rates can be found among miners, soldiers and swimming athletes. Healthy nails are usually protected from infestation. Previous damage such as injuries (including microtraumas), circulatory disorders or neuropathies promote the infection. Toenails are about five times more likely to be affected than fingernails.1

The majority of primary onychomycoses are caused by dermatophytes. These mushrooms feed on human keratin. They use strong proteolytic enzymes (keratinases) for this purpose.2 Yeasts and molds seem to play the role of secondary germs.2,3

The lateral distal edge of the nail is usually the entrance portal. The surface is seldom colonized. The infected nail loses its transparency and turns white to yellow. Subunguals form as the disease progresses Keratoses that can detach the nail plate from the bed. In extreme cases, the fungal infection can completely destroy the nail (crumb nail). The clinical picture is not specific. Before treatment, clinically similar nail diseases (nail psoriasis, eczema nail, nail dystrophy, etc.) must be ruled out and the diagnosis must be confirmed at least once with a native preparation and, if possible, with culture.

TREATMENT: Spontaneous healing is not to be expected. If there is no psychological stress and no risk of infection, e.g. from family members, nail mycosis can also remain untreated. The indication for therapy is to be set individually and after discussing the pros and cons. A disturbed aesthetic sensation also justifies treatment.

For reasons of tolerability, topical therapy is preferable to systemic therapy. Local treatment but only has a certain chance of success if certain requirements are met: Only a few - a maximum of five - nails are infected. The nail matrix is ​​free. A maximum of 30% (up to 50%) percent of the nail plate is affected. Patients must be able to apply the topping themselves.1 The lengthy treatment requires a lot of discipline and is therefore only suitable for motivated patients.

Two antifungal nail polishes with Amorolfin (LOCERYL; a-t 3 [1993], 26) respectively Ciclopirox (NAGEL BATRAFEN; a-t 8 [1994], 77) are offered. Like azole antimycotics and terbinafine (LAMISIL), amorolfine interrupts the biosynthesis of ergosterol, a component of the cell membrane of fungi. Ciclopirox is said to inhibit the absorption of essential substances into the fungal cell. The nail polishes must be used until sufficient healthy nails have grown back, usually six to twelve months. Toenails grow 0.5 to 1 mm per month,4 Fingernails a little faster. Amorolfin is applied once or twice a week,5 Ciclopirox initially every two days, later two, then once a week.6 Before painting, it is advisable to carefully remove the affected nail substance with a file or to remove it with nail scissors.

There are hardly any published clinical data. To the best of our knowledge, randomized placebo-controlled studies do not even exist. A meta-analysis of published and unpublished studies indicates clinically or mycologically confirmed cure rates with ciclopirox and amorolfine of 31% and 36%, respectively.7 The slightly higher rates in a much-cited study with amorolfine (46% to 52%) are due to the exclusion of more than a third of the participants from the analysis.8 Amorolfine nail polish can cause burning, itching, reddening of the skin, blisters and discoloration of the nail.5,9 In connection with ciclopirox varnish, redness and flaking are described.6 Systemic levels of active ingredients cannot be detected even with long-term use of Amorolfine varnish.5 No data are available on the systemic absorption of ciclopirox through the nail plate.6

Atraumatic onycholysis is a little shorter, but even more complex Bifonazole (MYCOSPOR) plus urea (MYCOSPOR nail set). Applied daily, the urea dissolves infected nail areas under an occlusive bandage. This generally takes two to three weeks but can take up to nine weeks.10 Then bifonazole alone must be applied daily for at least four weeks. Meaningful controlled studies have also not been published with bifonazole plus urea. In a small observational study, 12 weeks after the start of therapy, 63% of the affected nails were assessed as clinically and mycologically healed, 12 weeks later only 46%.11 In a comparative study with the additional intake of griseofulvin (FULCIN S and others), local therapy alone only brings about complete healing in 22% of cases.12

Urea can irritate and macerate the skin of the nail bed or edges and cause pain in the nail bed, and bifonazole can cause contact dermatitis. Inflammatory changes in the skin absorb 2% to 4% of the active ingredient after topical application.13

To systemic treatment Since 1993, in addition to griseofulvin, the naftifin derivative terbinafine (LAMISIL) and, since 1994, the azole antimycotic itraconazole (SEMPERA) have been offered by Nagelpilz. While the prescription of new products is increasing (SEMPERA rank 499, LAMISIL rank 585 of the most frequently prescribed drugs in 1997), the old product is practically no longer of any importance.14

Treatment with Griseofulvin we consider obsolete. Griseofulvin is only effective against dermatophytes. Because of its low affinity for keratin, it is not stored in the horny layers and must therefore be taken until the diseased nail grows out. Especially on the toenails it only brings low healing rates (17% to 25% in meta-analyzes).15,16 Griseofulvin has an immunogenic effect with allergic reactions, especially on the skin and liver. It can likely damage the genetic make-up.

Itraconazole and Terbinafine can be detected in the nail months after the end of therapy, while they are eliminated from the plasma within a few days or weeks.4 The agents therefore generally do not have to be taken for more than three months. In controlled studies with 250 mg terbinafine or 200 mg itraconazole daily for twelve weeks, healing rates of between 60% and 80% were achieved on toenails. The chances of success are greater if the big toenail is not affected.1,4 Fingernails respond with healing rates of up to 95 %.15 Even before starting systemic therapy, infected nail material should be removed atraumatically.

Whether terbinafine actually performs better, as it appears after two double and triple published, manufacturer-supported studies,17,18 needs to be confirmed in independent studies. Two smaller direct comparisons show no significant difference.19,20

The interval therapy approved in connection with itraconazole - 200 mg twice a day for one week, then a break for three weeks, repetition for a total of two to four months - reduces the total dose without impairing its effectiveness.21 An application for approval of this principle for terbinafine is not planned.22

The two antifungal drugs are not approved for children due to a lack of experience. For itraconazole, the manufacturer expressly excludes children and adolescents from treatment.23 Dosage recommendations are only available for the ineffective griseofulvin, which is not recommended for this group of patients because of its toxicity and potential mutagenicity. Given the soft nails of a child, the therapy is based on topical agents. In dermatological centers, children are also successfully treated with itraconazole in a dose adapted to their body weight.24,25 This requires special (documented) information for patients and their parents.

Gastrointestinal disorders, increases in liver enzymes and skin reactions are common with itraconazole and terbinafine with rates in the single-digit percentage range.26,27 Both antimycotics rarely cause severe harmful effects, especially on the liver and skin. In a post-marketing study, one in 5,000 suffers Terbinafine-User symptomatic liver damage (cf. a-t 1 [1993], 20).26 Erythema multiforme is described in one in 7,50028 the severe form with mucosal involvement (STEVENS-JOHNSON syndrome) and toxic epidermal necrolysis (LYELL syndrome) also occur (a-t 4 [1994], 40). At the first signs of a progressive rash, terbinafine must therefore be discontinued immediately. The drug can cause hypersensitivity reactions such as serum sickness and blood damage.

The risk of terbinafine affecting the taste (up to 3%)29 increases with age, lower body weight and with a history of loss of taste.26 The disorder often only resolves slowly after discontinuation. This can take up to two years.30 Taste disturbance can significantly reduce the quality of life. Before prescribing terbinafine, patients should be carefully informed about the potential risk.

With 25 suspicious transaction reports, terbinafine is the most frequently mentioned active ingredient in the NETWORK in connection with taste disorders (a-t 11 [1994], 109).

Also Itraconazole can cause symptomatic liver damage (a-t 8 [1992], 82): According to post-marketing data, however, no clinical hepatitis has been reported among more than 1.5 million users.31 The US product information, on the other hand, names three liver inflammations among more than 2,500 patients in connection with the intake of itraconazole (1: 850).29 Serious skin damage such as STEVENS-JOHNSON syndrome has also been described.29 Itraconazole, like other azole antifungals, inhibits the breakdown of drugs by liver CYP3A enzymes. Co-medication with antihistamines such as terfenadine (TELDANE et al .; a-t 1 [1997], 16) or the prokinetic cisapride (ALIMIX, PROPULSIN; a-t 7 [1998], 68) is contraindicated because of life-threatening cardiac arrhythmias. In the case of substances such as Ciclosporin A (SANDIMMUN), the dose may have to be reduced.

CONCLUSION: Before starting the treatment of nail mycoses, the patient must be informed about the requirements, the chances of success and the risks. The fungus should be detected at least once by native preparation, if possible also by culture. Mental impairment caused by the infection is a sufficient indication for treatment. However, therapy can also be omitted. The relatively tolerable local treatment, for example with Amorolfin nail polish (LOCERYL nail polish), places high demands on discipline and perseverance. There is a lack of valid data on the benefit assessment of external drugs. Probably at most every second to third person will be healed.

Systemic treatment leads to higher success rates, but is expensive and sometimes associated with unpleasant disruptive effects, for example loss of taste under terbinafine (LAMISIL), and rare life-threatening risks such as hepatitis or LYELL syndrome. According to the experience of our consultants, itraconazole (SEMPERA 7) is better tolerated than terbinafine. The method of choice is interval therapy with itraconazole - one week of intake followed by a three-week break - which significantly reduces the intake time and total dose.