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(a) A 47-year-old male with 52 recalcitrant facial flat warts during 8 years with topical retinoid, 5-fluorouracil, imiquimod and cryosurgery as previous treatments. (b) After treatment with isotretinoin at 30 mg/day for 12 weeks.
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Abstract Background: Recalcitrant facial flat warts are caused by human papillomavirus and may persist for years despite treatment. Isotretinoin has demonstrated benefits in the treatment of recalcitrant, genital and common warts, but placebo-controlled trials have not been performed.
Objective:
To determine whether isotretinoin is s...
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Some resistant warts, occasionally, do not
respond to treatment with Cryotherapy
alone. To the best of our knowledge, a
combination of ٨٥٪ Trichloroacetic Acid
(TCA) and Cryotherapy (C) for treatment
of resistant warts had not been studied in
the literature. The main objective is to determine
the efficacy and cure duration
when combining ٨٥٪ Trichl...
Citations
... 4 To date, it is known that oral isotretinoin administered at a dose of 0.5 mg/kg/day for 12 weeks is effective and safe for the treatment of recalcitrant facial flat warts. 5 Even with this dose, which is already considered low, different adverse effects reported like cheilitis, tiredness, nose bleeds, muscle aches and eyes problems are observed; because all adverse effects have a dosedependent behavior. 6 It is recommended to reduce the dose of isotretinoin in addition to changes in lifestyle and diet in case of increased levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycerides, cholesterol and creatine phosphokinase (CPK). ...
... The studies analyzed were prospective: three clinical trials, three case series, and two case reports Comparative studies included placebo, topical isotretinoin, and Candida antigen. 5,12,13 Only two carried out a histological study for diagnostic confirmation. 5,14 ...
... In the comparative studies, the treatment was administered for 12 weeks, in two of them (against placebo and isotretinoin gel respectively) the dose used was 0.5 mg/kg/day 5,12 and in the one compared against candida antigen it was 0.3 mg/kg/day. 13 Two studies assessed the efficacy of 0.5 mg/kg/day, in the first one the complete response (CR) was observed in 31 (100%) patients; in the second trial the complete response was assessed in 11 (69%) patients. ...
Background and Aims
The treatment of recalcitrant facial flat warts has always been challenging for dermatologists. The pain related to the application of the different treatments, side effects and costs are determining factors in the choice of therapy. To date, it is known that oral isotretinoin administered at a dose of 0.5 mg/kg/day is effective and safe; However, the different adverse effects reported have a dose‐dependent behavior and they could limit their use. Our aim is to assess the effect of low‐doses of oral isotretinoin to reducing side effects in the complete removal of recalcitrant facial flat warts and the current evidence in this regard.
Methods
An extensive literature review was conducted to identify articles relating to low doses of oral isotretinoin for recalcitrant flat warts treatment, regardless of design up to May 2023.
Results
The literature search yielded eight articles of 324 reviewed meeting criteria. Isotretinoin was administered in doses of 0.1–0.5 mg/kg/day. Complete elimination of the lesions occurred in 65.13% of the patients and a partial response in 19.26%. Four relapses were documented at the 4‐month follow‐up. The most frequent adverse effect was cheilitis.
Conclusion
We might consider low doses of oral isotretinoin for the treatment of recalcitrant facial flat warts in which side effects need to be reduced. However, current published works have several limitations, including small sample sizes, lack of control group and follow‐up periods. Larger, randomized, controlled studies are needed to verify the efficacy and safety of different doses of isotretinoin.
... In one study,16 patients treated with 30 mg/day of isotretinoin showed complete clearance of all recalcitrant flat warts within 12 weeks, while there was no improvement in the placebo group. 145 In the second study, patients who received a daily dose of oral isotretinoin at 0.5 mg/kg showed complete remission in 69% of cases. In contrast, only 38% of patients treated with topical isotretinoin 0.05% showed the same results after three months. ...
In 1982, the Food and Drug Administration (FDA) of the United States of America approved isotretinoin (13-cis-retinoic acid), a retinoid derivative of vitamin A, to treat severe recalcitrant acne vulgaris. Apart from its prescribed use for severe acne, evidence suggests that isotretinoin is commonly used off-label to treat mild-to-moderate acne, inflammatory skin conditions, genodermatoses, skin cancer, and other skin disorders. This is due to its anti-inflammatory, immunomodulatory, and antineoplastic properties. Some “off-label” use is successful, while others are ineffective. Therefore, this information is essential to clinicians for deciding on the appropriate use of isotretinoin. In this article, we aim to review the most updated evidence-based data about the use of oral isotretinoin in dermatology.
... One case of recurrence was observed after 2 months of follow-up in G1and no recurrence occurred in G2 or G3. Similar observations of absent or low recurrence rates have been reported by related studies with Candida Ag [9,18,21,[26][27][28]. ...
Immunotherapy represents a promising therapeutic option for treatment of warts. Different concentrations of Candida antigen (1/100 and 1/1000) and zinc sulfate 2% were not previously compared regarding their efficacy in treatment of cutaneous warts. The present study compared the safety and efficacy of intralesional candida antigen versus intralesional 2% zinc sulfate for treatment of cutaneous warts. This prospective controlled clinical trial included one hundred and five patients presented with common, plantar, and plane warts. Patients were divided randomly into three groups, each group included 35 patients. Group 1 were treated with intralesional candida antigen (Ag) 1/100, Group 2 were treated with intralesional candida Ag 1/1000, and Group 3 were treated with intralesional zinc sulfate 2%. This study found that target warts of group 1 displayed higher rate of complete clearance compared to group 2 and group 3 (94.3%, 77.1, 74.2%), respectively. The present study concluded that intralesional immunotherapy with Candida antigen was more effective than Intralesional 2% zinc sulfate in treatment of cutaneous warts and less painful . Clinical trial registration number is (Clinical Trials.gov Identifier: NCT03158168).
... An inverse relationship between the concentration of retinoids and the DNA of HPV in the infected keratinocytes has been demonstrated, suggesting a regulatory role on viral replication. 10,11 Isotretinoin has been recently used for the treatment of different types of cutaneous and genital warts with variable success rates. 4,5,12 However, there is no sharp discrimination or precise definitions of low and high doses have been established. ...
... Consequently, there are great variations in the dosing regimen without clear cut-off value in the available literature. Some authors used a fixed dose of 30 mg/day regardless the body weight, 11 and others used the common dose of 0.5 mg/kg/day. 13 Some studies used a low dose of 0.2 or 0.3 mg/kg/ day, 4,5 a high dose of 1 mg kg/day was used by other authors in three case reports. ...
Background:
Although oral isotretinoin has been considered as a potential therapeutic option for the treatment of different types of warts, the optimum dosage regimen is not yet well-established OBJECTIVE: To evaluate the efficacy and adverse effects of high versus low dose of oral isotretinoin in the treatment of cutaneous and genital warts.
Methods:
The study included 100 patients who were randomly assigned to two groups, 50 patients in each. Group 1 received 0.6 mg/kg/day (high dose isotretinoin) and group 2 received 0.3 mg/kg/day (low dose isotretinoin). In both groups, therapy was given daily until resolution was achieved or for a maximum of 3 months.
Results:
Complete clearance of warts was observed in 76% of the high dose isotretinoin group and in 46% of the low dose isotretinoin group. There was a statistically significant difference in the therapeutic response between the two groups. Recurrence was higher in the low dose group (26%) than the high dose group (7.8%). Adverse effects were mild and tolerable.
Conclusion:
High dose of systemic isotretinoin is more effective than low dose and seems to be a promising well-tolerated and effective therapeutic option for the treatment of cutaneous and genital warts. This article is protected by copyright. All rights reserved.
... One trial conducted in Japan [45] recruited patients with hepatitis C virus-related hepatocellular carcinoma, while three RCTs conducted in Greece [46], Mexico [47] and India [48], respectively, enrolled patients with genital or facial warts induced by HPV. They were orally administered peretinoin [45] or isotreninoin [46][47][48] each day for 3 [46][47][48] or 24 months [45], respectively. ...
... One trial conducted in Japan [45] recruited patients with hepatitis C virus-related hepatocellular carcinoma, while three RCTs conducted in Greece [46], Mexico [47] and India [48], respectively, enrolled patients with genital or facial warts induced by HPV. They were orally administered peretinoin [45] or isotreninoin [46][47][48] each day for 3 [46][47][48] or 24 months [45], respectively. The risk of bias was low for the Japanese study [45], while the other trials were at high risk of bias [46,48] or had some concerns [47] (Supplementary Table S2). ...
... One trial conducted in Japan [45] recruited patients with hepatitis C virus-related hepatocellular carcinoma, while three RCTs conducted in Greece [46], Mexico [47] and India [48], respectively, enrolled patients with genital or facial warts induced by HPV. They were orally administered peretinoin [45] or isotreninoin [46][47][48] each day for 3 [46][47][48] or 24 months [45], respectively. The risk of bias was low for the Japanese study [45], while the other trials were at high risk of bias [46,48] or had some concerns [47] (Supplementary Table S2). ...
Vitamin A (VA) deficiency is associated with increased host susceptibility to infections, but evidence on its role in the prevention and management of viral infections is still lacking. This review aimed at summarizing the effects of VA supplementation against viral infections to support clinicians in evaluating supplemental treatments. PubMed, Scopus, and Web of Science were searched. Randomized clinical trials comparing the direct effects of VA oral supplementation in any form vs. placebo or standard of care in the prevention and/or management of confirmed viral infections in people of any age were included. A narrative synthesis of the results was performed. The revised Cochrane Risk-Of-Bias tool was used to assess quality. Overall, 40 articles of heterogeneous quality were included. We found data on infections sustained by Retroviridae (n = 17), Caliciviradae (n = 2), Flaviviridae (n = 1), Papillomaviridae (n = 3), Pneumoviridae (n = 4), and Paramyxoviridae (n = 13). Studies were published between 1987 and 2017 and mostly conducted in Africa. The findings were heterogeneous across and within viral families regarding virological, immunological, and biological response, and no meaningful results were found in the prevention of viral infections. For a few diseases, VA-supplemented individuals had a better prognosis and improved outcomes, including clearance of HPV lesions or reduction in some measles-related complications. The effects of VA oral supplementation seem encouraging in relation to the management of a few viral infections. Difference in populations considered, variety in recruitment and treatment protocols might explain the heterogeneity of the results. Further investigations are needed to better identify the benefits of VA administration.
... Olguin et al. 17 used oral isotretinoin in the treatment of recalcitrant facial warts with promising results. He took a total of 31 patients with recalcitrant facial flat warts and divided them into two groups. ...
Background:
Plantar wart is a common viral infection of the plantar surface of the foot. Multiple treatment modalities are available but there is no definitive management option. The aim of this study is to compare topical adapalene gel 0.1% with cryotherapy in patients presenting with plantar warts in terms of time taken for complete clearance of the lesions.
Methods:
The study was conducted at the Department of Dermatology, PNS Shifa Hospital, Karachi from 28th April to 28th October 2020. Eighty-four patients with plantar warts who fulfilled the inclusion and exclusion criteria were included in the study. Approval from the institutional ethical review committee was sought and written informed consent was taken from all the patients. Patients were divided into two groups, A (Adapalene 0.1% gel) and B (Cryotherapy) of 42 patients each. Adapalene gel was applied twice daily under occlusion at home and cryotherapy was done at the clinic after every two weeks. Patients were followed weekly from the onset of treatment and days taken for complete clearance of plantar warts were noted. Both the groups were compared for the outcome, i.e., time taken for complete clearance of lesions.
Results:
The mean time for complete clearance of plantar warts in group A was 35.619±3.154 days and in group B, it was 50.404±3.178 days.
Conclusions:
Adapalene gel 0.1% used for the treatment of plantar warts helped in complete clearance of lesions faster than cryotherapy.
... Studies have also found that the HPV-DNA level is inversely proportional to the concentration of retinoids in the infected cells, and they also prevent cancer formation [3] in them. Systemic retinoids, mainly acitretin [4] and isotretinoin, [5,6] have shown complete resolution of recalcitrant and recurring warts in nongenital areas (common warts, verruca plana, and facial warts). Acitretin has also been used successfully in giant condyloma acuminate in combination with immunotherapy [7] or imiquimod and surgical debulking. ...
Genital warts caused by human papillomavirus are one of the most common sexually transmitted diseases seen in the outpatient department. Treatment modalities of genital warts vary depending on the size, site, extent of the lesions, and patient compliance. Here, we report a case of extensive genital warts managed with oral retinoids which resulted in complete clearance.
... There are some randomized controlled trials where oral isotretinoin was used as combination [18] and in monotherapy [19][20][21][22][23] to treat warts, also we found some case series (we only considered those with ≥ 10 patients and a minimum duration of 6 weeks of therapy) [24][25][26] and case reports [27][28][29][30][31][32][33][34][35] where oral retinoids other than isotretinoin alone or in combination with other treatment modalities have been used. Table 1 shows randomized controlled trials and case series where oral isotretinoin was used for treating anogenital warts. ...
Background
Anogenital warts are a common human papillomavirus infection. They cause emotional distress, especially when they are in the anogenital region. Cryotherapy is a first-line treatment. Previous clinical trials and case series have reported variable results with retinoids (isotretinoin) as adjuvant therapy.
Objective
To determine the safety and efficacy of low-dose oral isotretinoin as adjuvant treatment of anogenital warts.
Methods
Forty-six patients with anogenital warts were randomly assigned to isotretinoin + cryotherapy (n = 23) or only cryotherapy (n = 23). Patients were allocated via an interactive web-based randomization system. Evaluators were blinded to treatments. Isotretinoin 20 mg/daily + cryotherapy or cryotherapy were prescribed for 6 weeks. Patients were followed for 4 months. Genotyping of lesions was performed before treatment started. Dermatology Life Quality Index (DLQI) and Columbia-Suicide Severity Rating Scale (C-SSRS) were measured at the beginning and end of therapy. All patients completed the study.
Results
Both Groups had 50% clearance at the end of treatment. Recurrence in the combined group was not significantly lower than in the cryotherapy group (P = 0.59). Improvement was observed in the DLQI of all patients in both groups (P = 0.001). No suicidal intention was detected with the C-SSRS. Two patients (one in each group) had liver function test abnormalities after treatment.
Conclusion
Combined therapy showed a slight not significant efficacy for anogenital warts in Hispanic patients. Low-dose isotretinoin seems to be safe even when it is used with cryotherapy on anogenital warts.
Trial registration
On April 25, 2019 with registration number DE19-00004, CONBIOÉTICA-19-CEI-001–20160404. Prospectively registered.
... As previously mentioned, isotretinoin is suggested to inhibit the replication of HPV within infected cells, which may indicate its effectiveness in flat warts. Two RCTs [168,169], one prospective cohort study [170], and three case reports or series [171][172][173] of 88 total patients described the use of oral isotretinoin between 0.1 and 0.5 mg/kg/day to treat flat warts. Previously failed treatments included imiqimod, 5-fluorouracil, and cryosurgery [168,172]. ...
... Two RCTs [168,169], one prospective cohort study [170], and three case reports or series [171][172][173] of 88 total patients described the use of oral isotretinoin between 0.1 and 0.5 mg/kg/day to treat flat warts. Previously failed treatments included imiqimod, 5-fluorouracil, and cryosurgery [168,172]. Oral therapy was shown to be effective in providing patients complete clearance as soon as one month, with no relapse for follow-up periods ranging from four months up to three years [170,171,173]. Olguin-Garcia et al. compared 30 mg/day oral isotretinoin to a placebo control, presenting that 87.5% (n = 16) of patients had complete remission of facial flat warts, while no patients responded in the placebo group [168]. ...
... Oral therapy was shown to be effective in providing patients complete clearance as soon as one month, with no relapse for follow-up periods ranging from four months up to three years [170,171,173]. Olguin-Garcia et al. compared 30 mg/day oral isotretinoin to a placebo control, presenting that 87.5% (n = 16) of patients had complete remission of facial flat warts, while no patients responded in the placebo group [168]. One study compared the use of oral isotretinoin to a topical 0.05% formula, finding that oral therapy was significantly better than topical treatment [169]. ...
While isotretinoin has been the gold-standard of therapy for severe acne since its approval in 1982, its anti-inflammatory properties makes it a potentially applicable and versatile therapy for a wide variety of dermatologic conditions yet to be explored. This systematic review comprehensively recounts the success of oral isotretinoin in non-acne cutaneous diseases and provide insight into future directions of isotretinoin utility. A systematic literature review was performed using PubMed. Search terms included “isotretinoin” OR “accutane” AND “skin” OR “dermatology” OR “hair” OR “nails” OR “rosacea” OR “psoriasis” OR “pityriasis rubra pilaris” OR “condyloma acuminata” OR “granuloma annulare” OR “darier’s disease” OR “non-melanoma skin cancer” OR “frontal fibrosing alopecia” OR “cutaneous lupus erythematosus” OR “hidradenitis suppurativa” OR “photodamaged skin” OR “skin aging” OR “wart” OR “flat warts” OR “plane warts” OR “lichen planus” OR “dissecting cellulitis” OR “folliculitis decalvans” OR “sebaceous hyperplasia” OR “cutaneous t-cell lymphoma” OR “mycosis fungoides.” A total of 169 studies discuss the use of oral isotretinoin for 16 non-acne dermatologic conditions, the most common being non-melanoma skin cancers (0.2–8.2 mg/kg/day), cutaneous T-cell lymphomas (0.5–2 mg/kg/day), and rosacea (0.22–1 mg/kg/day). Inflammatory conditions such as rosacea, granuloma annulare, and hidradenitis suppurativa benefit from lower oral isotretinoin dosage of 0.3–1 mg/kg/day, whereas, hyperkeratotic diseases such as psoriasis and pityriasis rubra pilaris, consistently respond better to higher dosages of up to 2–4 mg/kg/day for lesion clearance. Recurrence of disease following discontinuation of isotretinoin have been reported for rosacea, psoriasis, granuloma annulare, Darier’s disease, dissecting cellulitis, and non-melanoma skin cancers. Disease exacerbation was reported in some patients with hidradenitis suppurativa. Off-label isotretinoin is an effective treatment choice for dermatological conditions beyond acne. Further prospective, randomized human trials are needed to clarify when and how to prescribe off-label isotretinoin for maximum efficacy and safety.
... The primary efficacy outcome was complete response, defined as complete disappearance of warts. 16 The secondary efficacy outcomes were nonresponse at initial site and recurrence rate during the study 12-week followup period. The primary safety outcome were clinical and biochemical outcomes as elevations of serum triglycerides/cholesterol and liver enzymes. ...
Background
The use of combined systemic retinoids and intralesional immunotherapy in the management of warts is still debatable without straightforward evidence.
Objective
Through network meta‐analysis, the current study evaluated the efficacy and safety of systemic retinoids alone or combined with other remedies in the treatment of warts.
Method
We searched six literature databases for clinical trials that compared systemic retinoids to local treatments or placebo in wart management. Outcomes were calculated as odds ratios (OR) with 95% confidence‐interval. We used the R software to perform conventional and network meta‐analyses (with a frequentist approach).
Results
Network meta‐analysis of eight trials showed that oral acitretin plus intralesional Candida Ag (OR=367.71), INF‐α plus oral isotretinoin (OR=223.77), oral acitretin (OR=117), Candida Ag (OR=91.93), oral isotretinoin (OR=62.26) and topical isotretinoin (OR=17.69) had higher complete recovery rates than placebo. Regarding the P‐score, oral acitretin plus intralesional Candida Ag had the highest efficacy in achieving complete response (P‐score=0.88), followed by INF‐α plus oral isotretinoin (P‐score=0.79), then oral acitretin (P‐score=0.60).
Limitations
Variable baseline characteristics and lack of data on some outcomes.
Conclusion
The current study shows the efficacy for systemic retinoids in the treatment of warts, especially reluctant or recurrent types. Moreover, combinations of systemic retinoids with intralesional immunotherapy yield higher rates of complete clearance with lower recurrence.
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