Oral antifungal medication for toenail onychomycosis.

BACKGROUND: Fungal infection of the toenails, also called onychomycosis, is a common problem that causes damage to the nail's structure and physical appearance. For those severely affected, it can interfere with normal daily activities. Treatment is taken orally or applied topically; however, traditionally topical treatments have low success rates due to the nail's physical properties. Oral treatments also appear to have shorter treatment times and better cure rates. Our review will assist those needing to make an evidence-based choice for treatment. OBJECTIVES: To assess the effects of oral antifungal treatments for toenail onychomycosis. SEARCH METHODS: We searched the following databases up to October 2016: the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, and LILACS. We also searched five trials registers and checked the reference lists of included and excluded studies for further references to relevant randomised controlled trials (RCTs). We sought to identify unpublished and ongoing trials by correspondence with authors and by contacting relevant pharmaceutical companies. SELECTION CRITERIA: RCTs comparing oral antifungal treatment to placebo or another oral antifungal treatment in participants with toenail onychomycosis, confirmed by one or more positive cultures, direct microscopy of fungal elements, or histological examination of the nail. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane. MAIN RESULTS: We included 48 studies involving 10,200 participants. Half the studies took place in more than one centre and were conducted in outpatient dermatology settings. The participants mainly had subungual fungal infection of the toenails. Study duration ranged from 4 months to 2 years.We assessed one study as being at low risk of bias in all domains and 18 studies as being at high risk of bias in at least one domain. The most common high-risk domain was 'blinding of personnel and participants'.We found high-quality evidence that terbinafine is more effective than placebo for achieving clinical cure (risk ratio (RR) 6.00, 95% confidence interval (CI) 3.96 to 9.08, 8 studies, 1006 participants) and mycological cure (RR 4.53, 95% CI 2.47 to 8.33, 8 studies, 1006 participants). Adverse events amongst terbinafine-treated participants included gastrointestinal symptoms, infections, and headache, but there was probably no significant difference in their risk between the groups (RR 1.13, 95% CI 0.87 to 1.47, 4 studies, 399 participants, moderate-quality evidence).There was high-quality evidence that azoles were more effective than placebo for achieving clinical cure (RR 22.18, 95% CI 12.63 to 38.95, 9 studies, 3440 participants) and mycological cure (RR 5.86, 95% CI 3.23 to 10.62, 9 studies, 3440 participants). There were slightly more adverse events in the azole group (the most common being headache, flu-like symptoms, and nausea), but the difference was probably not significant (RR 1.04, 95% CI 0.97 to 1.12; 9 studies, 3441 participants, moderate-quality evidence).Terbinafine and azoles may lower the recurrence rate when compared, individually, to placebo (RR 0.05, 95% CI 0.01 to 0.38, 1 study, 35 participants; RR 0.55, 95% CI 0.29 to 1.07, 1 study, 26 participants, respectively; both low-quality evidence).There is moderate-quality evidence that terbinafine was probably more effective than azoles for achieving clinical cure (RR 0.82, 95% CI 0.72 to 0.95, 15 studies, 2168 participants) and mycological cure (RR 0.77, 95% CI 0.68 to 0.88, 17 studies, 2544 participants). There was probably no difference in the risk of adverse events (RR 1.00, 95% CI 0.86 to 1.17; 9 studies, 1762 participants, moderate-quality evidence) between the two groups, and there may be no difference in recurrence rate (RR 1.11, 95% CI 0.68 to 1.79, 5 studies, 282 participants, low-quality evidence). Common adverse events in both groups included headache, viral infection, and nausea.Moderate-quality evidence shows that azoles and griseofulvin probably had similar efficacy for achieving clinical cure (RR 0.94, 95% CI 0.45 to 1.96, 5 studies, 222 participants) and mycological cure (RR 0.87, 95% CI 0.50 to 1.51, 5 studies, 222 participants). However, the risk of adverse events was probably higher in the griseofulvin group (RR 2.41, 95% CI 1.56 to 3.73, 2 studies, 143 participants, moderate-quality evidence), with the most common being gastrointestinal disturbance and allergic reaction (in griseofulvin-treated participants) along with nausea and vomiting (in azole-treated participants). Very low-quality evidence means we are uncertain about this comparison's impact on recurrence rate (RR 4.00, 0.26 to 61.76, 1 study, 7 participants).There is low-quality evidence that terbinafine may be more effective than griseofulvin in terms of clinical cure (RR 0.32, 95% CI 0.14 to 0.72, 4 studies, 270 participants) and mycological cure (RR 0.64, 95% CI 0.46 to 0.90, 5 studies, 465 participants), and griseofulvin was associated with a higher risk of adverse events, although this was based on low-quality evidence (RR 2.09, 95% CI 1.15 to 3.82, 2 studies, 100 participants). Common adverse events included headache and stomach problems (in griseofulvin-treated participants) as well as taste loss and nausea (in terbinafine-treated participants). No studies addressed recurrence rate for this comparison.No study addressed quality of life. AUTHORS' CONCLUSIONS: We found high-quality evidence that compared to placebo, terbinafine and azoles are effective treatments for the mycological and clinical cure of onychomycosis, with moderate-quality evidence of excess harm. However, terbinafine probably leads to better cure rates than azoles with the same risk of adverse events (moderate-quality evidence).Azole and griseofulvin were shown to probably have a similar effect on cure, but more adverse events appeared to occur with the latter (moderate-quality evidence). Terbinafine may improve cure and be associated with fewer adverse effects when compared to griseofulvin (low-quality evidence).Only four comparisons assessed recurrence rate: low-quality evidence found that terbinafine or azoles may lower the recurrence rate when compared to placebo, but there may be no difference between them.Only a limited number of studies reported adverse events, and the severity of the events was not taken into account.Overall, the quality of the evidence varied widely from high to very low depending on the outcome and comparison. The main reasons to downgrade evidence were limitations in study design, such as unclear allocation concealment and randomisation as well as lack of blinding.

Unusual Cause and Presentation of Collapsing Focal Segmental Glomerulosclerosis.

Collapsing focal segmental glomerulosclerosis (c-FSGS), a structural variant of focal segmental glomeruloslecrosis (FSGS), is considered to be the most aggressive FSGS form. Most patients present with severe nephrotic syndrome and often have rapidly progressing renal failure and progression to end-stage kidney disease. We are reporting a 28-year-old previously healthy woman, who was started on griseofulvin for onchomycosis; she subsequently developed acute renal failure with significant proteinuria. Exposure to the drug caused dramatic decline in the renal function. Renal biopsy was compatible with c-FSGS. To the best of our knowledge, this is the first case of biopsy-proven griseofulvin-associated c-FSGS. Our patient showed rapid improvement in renal function after discontinuation of griseofulvin. Universally, c-FSGS carries poor prognosis, but this case is unique because patient showed rapid improvement in renal function with a short duration after cessation of griseofulvin.

Probable Griseofulvin-Induced Drug Reaction with Eosinophilia and Systemic Symptoms in a Child.

A 9-year-old boy presented with fever, rash, anterior cervical lymphadenopathy, high liver enzymes, atypical lymphocytosis, and eosinophilia (drug reaction with eosinophilia and systemic symptoms [DRESS]). His history was notable for having taken griseofulvin for 3 weeks prior to onset of these findings. He improved after treatment with oral prednisone. We present a rare case of probable DRESS secondary to griseofulvin.

[Severe cutaneous drug reactions to misused griseofulvin: 2 cases]. / Deux cas de toxidermies graves secondaires à un mésusage de la griséofulvine.

BACKGROUND: Griseofulvin is an antifungal drug known to cause drug rash. However, it is widely prescribed outside its classic indications. Herein, we describe 2 cases in which griseofulvin was prescribed for off-label indications. PATIENTS AND METHODS: Case No. 1. A 51-year-old woman was referred to the department of internal medicine for management of Stevens-Johnson Syndrome (SJS). The symptoms appeared 17 days after she had taken griseofulvin for inguinal intertrigo. Case No. 2. A 19-year-old female patient consulted for toxic epidermal necrolysis (TEN) affecting 30% of her body surface, with a positive Nikolsky sign and severe mucosal lesions. These symptoms appeared 9 days after she began taking griseofulvin, which had initially been prescribed for her husband for mycosis. DISCUSSION: Toxic epidermal necrolysis, a condition chiefly of drug-related origin, is a severe mucocutaneous syndrome characterized by massive keratinocytic apoptosis. Although there are few scientific publications referring to griseofulvin-induced drug eruption, they deserve to be mentioned since this drug is widely used for purposes other than the approved indications and can cause life-threatening reactions. CONCLUSION: We report two cases of toxic epidermal necrolysis related to the misuse of griseofulvin. It is important to bear in mind the precautions for use of oral antifungal drugs, which are strictly reserved for use against resistant or diffuse forms of mucocutaneous fungal infections.

[Generalized exanthematous pustular dermatophytid, a rare clinical presentation of dermatophytid reaction]. / La dermatophytide exanthématique et pustuleuse généralisée (DEPG), une présentation clinique rare de dermatophytide.

BACKGROUND: Dermatophytids are immunologically mediated dermatologic presentations secondary to sensitization to a dermatophyte infection. They are most frequently associated with toe-web intertrigo and usually present as localized, palmar, pruriginous vesicular eruptions. We report three original cases of generalized exanthematous pustular dermatophytid associated with kerions. PATIENTS: Two boys aged 11 and 6 years, and one girl aged 6 years initially presented with kerion secondary to Trichophyton tonsurans (case 1), Trichophyton soudanense (case 2) and Trichophyton mentagrophytes (case 3), respectively. Two to three days after initiation of griseofulvin treatment, all patients presented with a pustular eruption extending from the head to the trunk, associated in one case with fever of 39°C and inflammatory chondritis. Samples obtained from the pustular lesions were sterile, serum inflammatory markers were within the normal range and skin lesions resolved on oral corticosteroid treatment (prednisone 0.75 mg/kg, case 1) or high-potency topical steroids (cases 2 and 3) given as an adjunct to griseofulvin treatment (19 to 23 mg/kg/d). DISCUSSION: Dermatophytids occur during the acute phase of infection or within a few days of treatment initiation. Lesions are remote from the infection site, contain no dermatophyte, and resolve after treatment of the infection. We report three original cases of generalized exanthematous pustular dermatophytid, associated in one case with fever and inflammatory chondritis. The main differential diagnosis is acute generalized exanthematous pustulosis secondary to antifungal drugs. Differences in clinical presentation between the two enable the appropriate diagnosis to be made as well as continued use of the antifungal medication needed to cure the patient. General or topical steroids may also be used in combination.

Protective action of antioxidants on hepatic damage induced by griseofulvin.

Erythropoietic protoporphyria (EPP) is a disease associated with ferrochelatase deficiency and characterized by the accumulation of protoporphyrin IX (PROTO IX) in erythrocytes, liver, and skin. In some cases, a severe hepatic failure and cholestasis were observed. Griseofulvin (Gris) develops an experimental EPP with hepatic manifestations in mice such as PROTO IX accumulation followed by cellular damage as wells as necrotic and inflammatory processes. The antioxidant defense system was also altered. The aim was to evaluate the possible protective effect of different antioxidant compounds: trolox (Tx), ascorbic acid (Asc), the combination Tx and Asc, melatonin (Mel), and the polyphenols: ellagic acid, quercetin, chlorogenic acid, caffeic acid, gallic acid, and ferulic acid on liver damage and oxidative stress markers in a mouse model of EPP. Coadministration of Gris with Tx, Asc, and its combination, or Mel mainly affected heme biosynthetic pathway, resulting in a decrease in ALA-S activity which was increased by Gris, while the tested polyphenols exerted a protective effect on oxidative stress, decreasing lipid peroxidation and the activity of some antioxidant enzymes. In conclusion, antioxidant compounds can only protect partially against the liver damage induced by Gris, reducing oxidative stress or acting on heme regulation.

Meta-analysis of randomized, controlled trials comparing particular doses of griseofulvin and terbinafine for the treatment of tinea capitis.

Two oral antifungal agents, griseofulvin and terbinafine, have regulatory approval in the United States, but it is unknown whether one has superior overall efficacy. Genus-specific differences in efficacy are believed to exist for the two agents. It is not clear at what doses and durations of treatment these differences apply. The goals of this meta-analysis were to determine whether a statistically significant difference in efficacy exists between these agents at a given dose and duration of each in tinea capitis infections overall and to determine whether a genus-specific difference in efficacy exists for these two treatments at a given dose and duration of each. We performed a literature search for clinically and methodologically similar randomized controlled trials comparing 8 weeks of griseofulvin (6.25-12.5 mg/kg/day) to 4 weeks of terbinafine (3.125-6.25 mg/kg/day) in the treatment of tinea capitis. A meta-analysis was performed using the Mantel-Haenszel method and random effects model; results were expressed as odds ratios with 95% confidence intervals. Meta-analysis of randomized controlled trials did not show a significant difference in the overall efficacy of the two drugs at the doses specified, but specific efficacy differences were observed based on the infectious species. For tinea capitis caused by Microsporum spp., griseofulvin is superior (p = 0.04), whereas terbinafine is superior for Trichophyton spp. infection (p = 0.04). Our results support species-specific differences in treatment efficacy between griseofulvin and terbinafine and provide a clinical context in which this knowledge may be applied.

Impairment of heme biosynthesis induces short circadian period in body temperature rhythms in mice.

It has been demonstrated that the function of mammalian clock gene transcripts is controlled by the binding of heme in vitro. To examine the effects of heme on biological rhythms in vivo, we measured locomotor activity (LA) and core body temperature (T(b)) in a mouse model of porphyria with impaired heme biosynthesis by feeding mice a griseofulvin (GF)-containing diet. Mice fed with a 2.0% GF-containing diet (GF2.0) transiently exhibited phase advance or phase advance-like phenomenon by 1-3 h in terms of the biological rhythms of T(b) or LA, respectively (both, P < 0.05) while mice were kept under conditions of a light/dark cycle (12 h:12 h). We also observed a transient, ~0.3 h shortening of the period of circadian T(b) rhythms in mice kept under conditions of constant darkness (P < 0.01). Interestingly, the observed duration of abnormal circadian rhythms in GF2.0 mice lasted between 1 and 3 wk after the onset of GF ingestion; this finding correlated well with the extent of impairment of heme biosynthesis. When we examined the effects of therapeutic agents for acute porphyria, heme, and hypertonic glucose on the pathological status of GF2.0 mice, it was found that the intraperitoneal administration of heme (10 mg·kg(-1)·day(-1)) or glucose (9 g·kg(-1)·day(-1)) for 7 days partially reversed (50%) increases in urinary δ-aminolevulinic acids levels associated with acute porphyria. Treatment with heme, but not with glucose, suppressed the phase advance (-like phenomenon) in the diurnal rhythms (P < 0.05) and restored the decrease of heme (P < 0.01) in GF2.0 mice. These results suggest that impairments of heme biosynthesis, in particular a decrease in heme, may affect phase and period of circadian rhythms in animals.

Guidelines for the management of tinea capitis in children.

Practice guidelines for the treatment of tinea capitis (TC) from the European Society for Pediatric Dermatology are presented. Tinea capitis always requires systemic treatment because topical antifungal agents do not penetrate the hair follicle. Topical treatment is only used as adjuvant therapy to systemic antifungals. The newer oral antifungal agents including terbinafine, itraconazole, and fluconazole appear to have efficacy rates and potential adverse effects similar to those of griseofulvin in children with TC caused by Trichophyton species, while requiring a much shorter duration of treatment. They may be, however, more expensive (Grading of recommendation A; strength of evidence 1a). Griseofulvin is still the treatment of choice for cases caused by Microsporum species. Its efficacy is superior to that of terbinafine (Grading of recommendation A; strength of evidence 1b), and although its efficacy and treatment duration is matched by fluconazole (Grading of recommendation A; strength of evidence 1b) and itraconazole (Grading of recommendation A; strength of evidence 1b), griseofulvin is cheaper. It must be noted, however, that griseofulvin is nowadays not available in certain European countries (e.g., Belgium, Greece, Portugal, and Turkey).

Pharmaceuticals that cause mammary gland tumors in animals: findings in women.

Risk of breast cancer in women was assessed for eight pharmaceuticals that produce mammary tumors in experimental animals, using nested case-control analyses in two cohorts with prescription records in a comprehensive medical care program. The two cohorts were: (1) earlier cohort: 78,118 female members who received prescriptions in 1969-1973, of whom 2,467 developed breast cancer, and (2) later cohort: 3,289,408 female members who received prescriptions in 1994-2006 of whom 24,528 developed breast cancer. Longest follow-up was until June 30, 2006. Ten randomly selected concurrent control women were age-matched to almost every case. Relative risks were estimated by conditional logistic regression. Case ascertainment was lagged by 2 years, or unlagged and subdivided by number of prescriptions received. Some analyses were controlled for hormone use and sensitivity analyses were conducted to estimate the effects of uncontrolled confounding. In the later cohort furosemide, and metronidazole showed statistically significant but very small increases in relative risk (ranging from 1.07 to 1.13). Of these, only furosemide showed increased risk in the earlier cohort: 2-year lag relative risk 1.66 (95% confidence interval 1.23-2.24) or as low as 0.97, assuming uncontrolled positive confounding. Griseofulvin showed significant increases in the later cohort: relative risk for three or more prescriptions 1.48 (1.08-2.03) or as low as 1.23 assuming uncontrolled positive confounding and non-significant increases were noted in the earlier cohort. Our findings are limited by their inconsistency across the two cohorts and our inability to directly control for most established breast cancer risk factors. Although inconclusive, our findings suggest a need for more research on furosemide and griseofulvin.

Griseofulvin: a teratogenic study.

Griseofulvin, a fungistatic agent, was administered in oral doses of 125 to 1500 milligrams per kilogramn per day to pregnant rats during organogenesis. Evaluation of the offspring from dams treated with the largest doses, 63 and 75 times a therapeutic dose in man, indicated decreased survival rates and a syndrome of malformations.

Fungal nail infections: diagnosis and management.

1) Fungal nail infection, or onychomycosis, mainly affects toenails. Infections are generally asymptomatic. Spontaneous regressions, but also complications, appear to be rare. Discomfort and cosmetic complaint are occasionally reported; 2) After a review of the literature based on the standard Prescrire procedure, we examined the diagnosis and management of fungal nail infections; 3) Clinical signs of fungal nail infections are non-specific. Alternative diagnoses include psoriasis and nail microtrauma. Nail hyperkeratosis and leukonychia are useful diagnostic pointers. Matrix involvement has important implications in the choice of treatment; 4) Detection of fungal structures by direct examination of a nail sample is strongly suggestive of fungal nail infection. In contrast, cases of negative direct examination with positive culture must be interpreted with caution, as contamination is frequent; 5) Antifungal lacquers (5% amorolfine and 8% ciclopirox) applied to the nails cure about 30% of fungal infections and sometimes cause mild irritation. There is no firm evidence that these solutions are any more effective than other topical antifungals applied daily to the affected nail. Trimming, filing or grinding the nail, in addition to these drug treatments, is likely to be beneficial, but these measures have not been evaluated; 6) Chemical nail destruction with a combination of urea and bifonazole, followed by treatment with an antifungal ointment, can be used when the nail is markedly thickened. Non-comparative trials have shown cure rates close to 70% at three months when the matrix is not involved, and 40% with matrix involvement. Drug application is inconvenient and local reactions are frequent. Surgical nail avulsion carries a risk of local infection and permanent nail dystrophy; 7) Oral terbinafine is effective in more than 50% of cases but its cutaneous, hepatic and haematological adverse effects are severe in about 1 in 2000 patients and can be life-threatening; 8) It is better to treat Candida nail infections with oral azoles (ketonazole, itraconazole) than with terbinafine. These treatments carry a risk of serious adverse effects and numerous drug interactions; 9) Fungal nail infections are usually mild. Treatments with potentially severe adverse effects must therefore be used with caution. It is better not to treat fungal nail infections if the risks outweigh the expected benefits.

Terbinafine hydrochloride oral granules versus oral griseofulvin suspension in children with tinea capitis: results of two randomized, investigator-blinded, multicenter, international, controlled trials.

BACKGROUND: Although griseofulvin is currently considered the primary antifungal agent used to treat tinea capitis in many countries, increasingly higher doses and longer durations of treatment are becoming necessary to achieve effective treatment. Alternative antifungal therapies with shorter/simpler treatment regimens may be important to develop for this indication. OBJECTIVE: To compare the efficacy and safety of a new pediatric formulation of terbinafine hydrochloride oral granules with griseofulvin oral suspension in the treatment of tinea capitis. METHOD: Children (4-12 years of age) with clinically diagnosed and potassium hydroxide microscopy-confirmed tinea capitis were randomized in two identical studies (trial 1, trial 2) to once-daily treatment with terbinafine (5-8 mg/kg; n = 1040) or griseofulvin administered per label (10-20 mg/kg; n = 509) for a period of 6 weeks followed by 4 weeks of follow-up. End-of-study complete cure (negative fungal culture and microscopy with Total Signs and Symptoms Score [TSSS] = 0), and mycologic (negative culture and microscopy) and clinical cure (TSSS = 0) were primary and secondary efficacy variables, respectively. Efficacy analysis was based on pooled data using modified intent-to-treat population (those who received at least one dose of study drug and had positive baseline fungal culture, N = 1286). Safety assessments included monitoring of the frequency and severity of adverse events (AEs). RESULTS: Rates of complete cure and mycologic cure were significantly higher for terbinafine than for griseofulvin (45.1% vs 39.2% and 61.5% vs 55.5%, respectively; P < .05). A majority (86.7%) of patients received griseofulvin, 10 to 19.9 mg/kg per day; complete cure rate was not found to be higher among patients who received griseofulvin more than 20 mg/kg per day compared with those who received less than 20 mg/kg per day. Complete cure rate was statistically significantly greater for terbinafine compared to griseofulvin in trial 1 (46.23% vs 34.01%) but not in trial 2 (43.99% vs 43.46%). On the basis of pooled data, clinical cure was higher for terbinafine than for griseofulvin, but the difference was not found to be statistically significant (P = .10). Subgroup analyses revealed that terbinafine was significantly better than griseofulvin for all cure rates--mycologic, clinical, and complete--among patients with Trichophyton tonsurans but not Microsporum canis (P < .001). For M. canis, mycologic and clinical cure rates were significantly better with griseofulvin than with terbinafine (P < .05). Approximately 50% of patients in each group reported an AE; almost all were mild or moderate in severity. Nasopharyngitis, headache, and pyrexia were most common in both groups. There were no drug-related serious AEs, no deaths, and no significant effects on weight or laboratory parameters, including liver transaminases. LIMITATIONS: In retrospect, a difference in the distribution of infecting microorganisms between the two trials was a limitation. Stringent adherence to griseofulvin doses recommended by prescribing information but smaller than those used in current clinical practice, and exclusion of adjuvant therapies such as shampoos or topical agents, which are routinely used in practice, are other limitations. CONCLUSIONS: Data from this largest pediatric trial of terbinafine to date indicate that terbinafine is efficacious and well tolerated in the treatment of tinea capitis. Terbinafine is an effective alternative to griseofulvin against T. tonsurans tinea capitis.

Griseofulvin and/or Terbinafine Induced Toxic Epidermal Necrolysis in an Adult Female Patient - A Case Report.

An 18 years old female patient, who was taking treatment for tinea cruris developed Toxic Epidermal Necrolysis (TEN) due to therapeutic dose of griseofulvin with concomitant use of terbinafine. Both the drugs were stopped; patient's condition was gradually improved after starting the treatment. As per WHO-UMC causality assessment criteria, association between reaction and drug was possible (for both griseofulvin and terbinafine). Griseofulvin and terbinafine, both are widely used as an oral antifungal agent to treat fungal infections, careful monitoring is required in the initial periods of the treatment to prevent such type of serious adverse drug reaction. We report a case of TEN possibly caused by griseofulvin with concomitant use of terbinafine resulting in diagnostic difficulty.

Treatments for Cutaneous Lichen Planus: A Systematic Review and Meta-Analysis.

BACKGROUND: Cutaneous lichen planus (CLP) is an inflammatory dermatosis. Its chronic relapsing course and frequently spontaneous regression hamper the assessment of treatment effectiveness. OBJECTIVE: To evaluate the efficacy of available treatment modalities for CLP. DATA SOURCES: PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), ClinicalTrials.gov registry. METHODS: We performed a systematic review of the current literature. All randomized controlled trials, nonrandomized case-control studies, and cohort studies with more than one treatment arm were included. The primary outcomes were complete response and time to complete response. The secondary outcomes were partial response, relapse, time to relapse, reduction of itch, the adverse event rate, and withdrawal due to adverse events. DATA SYNTHESIS: Sixteen studies met the inclusion criteria, of which 11 were randomized controlled trials. Most trials had a small sample size. In the rare studies in which variants other than generalized or classic lichen planus were included, they could not be analyzed separately. Body-of-evidence quality ranged from very low to moderate. Acitretin, sulfasalazine, and griseofulvin were associated with increased overall response rates in comparison with placebo. Narrow-band ultraviolet B radiation (NBUVB) was more effective than 6 weeks' low-dose prednisolone in achieving a complete response, and prednisolone was more effective than enoxaparin. Hydroxychloroquine was more effective than griseofulvin in achieving an overall response. Betamethasone valerate 0.1% ointment had comparable efficacy to calcipotriol ointment. Methotrexate was effective, with a nonsignificant difference in the complete response rate in comparison with oral betamethasone. In nonrandomized controlled trials, oral psoralen plus ultraviolet A photochemotherapy (PUVA) had comparable efficacy to a PUVA bath and NBUVB. Psoralen plus sunlight exposure (PUVASOL) and betamethasone dipropionate 0.05% cream were effective relative to a short course of oral metronidazole. CONCLUSIONS: Several effective treatment options are available for CLP. Further well-designed studies are warranted to investigate the efficacy of topical glucocorticoids-the current first-line therapy-as well as other treatment modalities, and the treatment of different variants of CLP.

Griseofulvin causing hyperhemopexinemia and hepatic proliferation in mice: an in vivo and in vitro study.

Concentrations of hemopexin, a porphyrin-binding serum protein synthesized exclusively in the liver, increased significantly and concomitantly with levels of erythrocyte and liver protoporphyrin and coproporphyrin in mice made porphyric with 1% griseofulvin in the feed. Liver weights of porphyric mice increased remarkably. In comparison with controls, the ratio of the weight of normal to porphyric livers was at 10 days 1:2.1, at 21 days 1:2.8, and at 46 days 1:3.8. This increase in liver size was accompanied by increased cell division. The hepatic hyperplastic tissue fragments survived in vitro for several weeks and could be subcultured. The cultured cells, like those of the original liver, showed intense protoporphyrin fluorescence in the cytoplasm.