Journal of Dermatological Treatment

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Dermatological indications for the use of

isotretinoin beyond acne

Emily Forbat, Faisal R. Ali & Firas Al-Niaimi

To cite this article: Emily Forbat, Faisal R. Ali & Firas Al-Niaimi (2018) Dermatological indications
for the use of isotretinoin beyond acne, Journal of Dermatological Treatment, 29:7, 698-705, DOI:
10.1080/09546634.2018.1445194

To link to this article: https://doi.org/10.1080/09546634.2018.1445194

Published online: 14 Mar 2018.

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JOURNAL OF DERMATOLOGICAL TREATMENT
2018, VOL. 29, NO. 7, 698–705
https://doi.org/10.1080/09546634.2018.1445194

REVIEW ARTICLE

Dermatological indications for the use of isotretinoin beyond acne

Emily Forbata, Faisal R. Alib and Firas Al-Niaimib
a
Chelsea and Westminster Hospital, London, UK; bDermatological Surgery & Laser Unit, St John’s Institute of Dermatology, Guy’s Cancer Centre,
Guy’s and St Thomas’ NHS Foundation Trust, London, UK

ABSTRACT ARTICLE HISTORY

While the use of isotretinoin has revolutionized the treatment of acne vulgaris, isotretinoin is increasingly Received 3 February 2018
recognized as a useful therapeutic option for many other cutaneous conditions. We review the evidence Accepted 14 February 2018
underlying the use of isotretinoin for a variety of dermatological indications including hidradenitis suppu-
KEYWORDS
rativa, sebaceous gland pathology, rosacea, scarring alopecia, cosmetic dermatology, and non-melanoma
Isotretinoin; retinoids;
skin cancer prophylaxis amongst other uses, and thus consider alternative uses within dermatology prac- rosacea; cosmetic
tice. The studies found benefit of isotretinoin, however most trials lacked statistical power and in many dermatology; hidradenitis
cases the use was limited to case series. Isotretinoin, if used within the correct cohort with appropriate suppurativa
pretreatment counseling regarding side-effects, is a well-tolerated medication with potential as either an
adjunctive treatment or a second-line agent in those recalcitrant cases unresponsive to first-line therapy.

Introduction 33 case studies/case series (6,7,9–39), two retrospective reviews

Isotretinoin, also known as 13-cis-retinoic acid, is a synthetic drug
best known for its treatment of acne (1). The mechanism of action
results from isotretinoin-induced expression of apoptotic protein
necrosis factor, and a recent review suggests that apoptosis is the
culprit for the multitude of well-known side-effects of isotretinoin
(2). Isotretinoin regulates cell proliferation by binding to nuclear
retinoic acid receptors. Furthermore, it is said to decrease poly-
amine synthesis and keratinization which contributes to its anti-
inflammatory and anti-prolific properties (3). Isotretinoin was first
approved for the treatment of acne in 1982 (4). The UK license for
isotretinoin was first established in 2001, and the European direct-
ive advises the treatment of acne to start at a dose of 0.5 mg/kg
and be avoided in children under 12 years old, with strict preg-
nancy prevention strategies. Furthermore, liver function and lipid
monitoring are required to be checked prior to treatment,
1 month post-initiation of treatment, and 3 months thereafter (5).
The longest duration of use of isotretinoin from our review was 7
years, in which low-dose isotretinoin was used intermittently to
treat erythema dyschromicum perstans (6). The age range of
patients reviewed in this article varied from just under 7 months
of age to 64 years old (7,8).
Method
We conducted a literature search in October 2017, to review the
current uses of isotretinoin in dermatology beyond the treatment
of acne. A PubMed, search was carried out, with the search criteria
‘Isotretinoin’ & ‘Dermatology’. Only articles published in English
were included. Review articles were omitted, unless they specific-
ally analyzed studies within them. Articles on the use of isotreti-
noin and acne were also excluded.
Results
Our search identified 1125 studies, of which 49 met the criteria of
assessing the use of isotretinoin beyond acne. In total, there were
(8,40), six randomized control trials (RCTs) (41–46), two random-
ized comparative trials (47,48), one open-label non-randomized
prospective pilot study (49), one retrospective comparison study
(50), one single-blind randomized study (51), two case-controlled
randomized clinical studies (52,53), and one cohort study (54).
Within these studies, 2996 patients were treated between 1985
and 2017 (Table 1).
Hidradenitis suppurativa
A retrospective review has been carried out assessing the use of
isotretinoin for the treatment of hidradenitis suppurativa (HS) (39).
There have been a multitude of papers which refute the benefit
of isotretinoin in patients with concomitant HS and acne (56,57).
Treatment with isotretinoin in these cases of dual pathology often
demonstrated a minimal response of HS, despite both HS and
acne both being associated with ductal abnormalities (58). Huang
and Kirchhof argue that isotretinoin should not be dismissed, as
careful literature evaluation in fact demonstrates that in the cor-
rect cohort – i.e. those with mild/moderate HS, females, or con-
comitant acne – complete remission has been achieved (8).
Further research is required, as the use of isotretinoin in HS is
sparse.
Sebaceous gland pathology
A randomized comparative trial comparing alternate daily use of
10 mg isotretinoin versus topical anti-seborrheic treatment in
moderate to severe seborrhea and seborrheic dermatitis (N ¼ 45)
over 6 months, demonstrated a significantly greater reduction in
scalp sebum secretion (p ¼ .004) in the isotretinoin arm after 3
months (47). Patients were not followed-up beyond 3 months and
the dosage was not weight-dependent. Tagliolatto et al. treated
20 patients with sebaceous hyperplasia with isotretinoin (1 mg/kg
per day) for 2 months; the average number of skin lesions
decreased from 24 to 2 per patient (p < .05) (59). Isotretinoin is

CONTACT Dr Emily Forbat emilyforbat@gmail.com Chelsea and Westminster Hospital, 369 Fulham Rd, London SW10 9NH, UK
ß 2018 Informa UK Limited, trading as Taylor & Francis Group
Table 1. Studies on the use of isotretinoin beyond acne.
Study
Part 1: Inflammatory dermatoses and infectious disorders
Inflammatory dermatoses
Huang and Kirchhof (8)
Rademaker (40)
Sbidian et al. (41)
Rallis and Korfitis (20)
Uslu et al. (22)
Gollnick et al. (52)
Mortazavi et al. (51)
Al-Shobaili and Al-
Khenaizan (30)
Infectious disorders
Al-Hamamy, Salman and
Abdulsattar (19)
Indication Aim Patient number Dose Findings
Hidradenitis A retrospective N ¼ 25 0.45 ± 0.20 mg/kg/day for 6.8 ± 4.3 32% no response,
suppurativa chart review months 32% partial response,
36% complete response
Papulopustular A retrospective N ¼ 52 20 mg isotretinoin/day 12% did not attend follow up.
rosacea review reduced to 10–20 mg once to five Those that did attend, 91% (42/46): rosacea cleared or
times a week in 67%, was excellent.
or One patient stopped due to SE.
increased in 15% (who all had add- 44% no SE.
itional acne) to 30–40 mg/day The most common SE was cheilitis in 52%, which was
mild in all but one patient
Papulopustular A RCT N ¼ 156 0.25 mg/kg/day Post 4-month treatment at least 90% reduction of pap-
rosacea versus ules/papules in comparison to pre-treatment.
placebo for 4 months Significantly higher skindex score in treated group versus
placebo group.
58.3% of 51 patients who agreed to 4 month FU, demon-
strated relapse
Granulomatous A case study N¼1 0.7 mg/kg/day for 24 weeks. 3-month FU: satisfactory
rosacea 5-month FU: total remission
6-month post-cessation of treatment: no recurrence.
Rosacea A case series N ¼ 25 20 mg/day for 4 months, tapering the Papule and pustule, erythema index, sebum level,
dose within the following 6 months. dermatologist’s and patient’s erythema scores, and
dermatologist’s sebum scores: significantly lower, one-
month post-therapy versus pre-therapy (p < .05).
45% relapse within median FU of 11 months
Rosacea Doxycycline- and placebo- N ¼ 573 One of three different dosages of iso- Isotretinoin 0.3 mg/kg most effective dose versus placebo.
controlled, randomized tretinoin With IST:
clinical study  0.1 mg Complete remission in 24% (14%)
 0.3 mg Marked improvement 57% (55%) versus the bracketed fig-
 0.5 mg ures for doxycycline
(per kg body weight) SE: increase incidence of dermatitis facialis with 0.5 mg/kg
þ
doxycycline (100 mg daily for 14 days,
then 50 mg daily)
or placebo
for 12 weeks.
Psoriasis vulgaris A single blind N ¼ 37 Intervention group: narrow band ultra- Psoriasis Area Severity Index (PASI) scores demonstrated
randomized violet B (NBUVB) þ isotretinoin no significant difference between efficacies of two
clinical study (0.5 mg/kg/day) treatments
Control group: narrow band ultraviolet But
B (NBUVB) þ isotretinoin Isotretinoin þ NBUVB can reduce phototherapy sessions
(0.5 mg/kg/day) and cumulative NBUVB dose required.
Pustular psoriasis A case study N¼1 Initially started on methotrexate No relapse after methotrexate stopped after the isotreti-
15 mg/week for 6 weeks, (relapsed noin was commenced.
when methotrexate was reduced.) Excellent control when isotretinoin continued at 40 mg/
Therefore, day in conjunction with topical steroids.
40 mg/day per oral (0.75 mg/kg/day)
isotretinoin was added, and 3 weeks
later methotrexate was stopped.
JOURNAL OF DERMATOLOGICAL TREATMENT
Plane Warts A case series N ¼ 26 Mean of 0.5 mg/kg/day for 2 months. 73.07% complete response
26.92% no response at the end of treatment.
78.94% who had complete response, no recurrence at 4-
month follow up
699
(continued)
Table 1. Continued
Study
Georgala et al (44)
Yildirim et al. (34)
Part 2: Cosmetic, sebaceous gland pathology and scarring alopecia
Cosmetic
Bagatin et al. (48)
Bagatin et al. (42)
Rabello-Fonseca et al. (29)
Sebaceous gland pathology
De Souza Leao Kamamoto,
et al. (47)
Gupta et al. (7)
Liu et al. (14)
Jung et al. (15)
700
Indication Aim Patient number Dose Findings
Condylomata acumi- A randomized Placebo- N ¼ 60 Randomly assignment to receive Group 1:
nata of the cervix controlled trial Group 1: isotretinoin, 0.5 mg/kg daily  32.1% responded completely
for 12 weeks  39.2% responded partially
Group 2: placebo  28.5% did not respond
Group 2:
 0% responded completely
 8% responded partially
E. FORBAT ET AL.
 92% did not respond
Oral isotretinoin demonstrated significant difference in
treatment outcome.
Condyloma A case study N¼1 IFNalfa-2a (three million unit’s S/C, 3/ Clearance at 3 months, no recurrence at 1 year FU.
acuminatum week) þ oral isotretinoin (0.5 mg/kg/ SE: mild chelitis
day) for 2 months.
IFNalfa stopped at 2 months and IST
continued for a further month.
Photo-aging A randomized, N ¼ 24 12 people treated with 20 mg/day Qol scores reduced for all subjects.
comparative study 12 treated with Retinoic acid cream for Histology:
6 months  Corneal layer diminution
 Epidermal thickness increase
 Elastosis reduction.
No significant difference between groups
Photo-aging A RCT N ¼ 32 Group A: 20 mg isotretinoin 3/week- Significant difference in p53 between groups, major
þ moisturizer/sunscreen for 3 reduction in p53 in group A.
months Authors felt this reduction reinforced retinoid chemopre-
Group B: moisturizer/sunscreen only vention.
Not thought to be effective in photo aging
Photo-aging A case series N ¼ 33 Group 1: Statistically significant increase in collagen fibers with
10 mg isotretinoin both regimes
Group 2: Mean, 37.8%, increasing to 44.4%; p ¼ .029 with the 10-
20 mg 3/week for 3 months mg dosage
Mean, 36.6%, increasing to 41.9%; p ¼ .01 with the 20-mg
dosage.
Overall improvement in texture, wrinkle depth, and skin
coloration.
Limitation: no placebo control group
Seborrhea and seb- A Randomized N ¼ 45 Group Isotretinoin (ISO): Rate of sebum production significantly decreased in
orrheic dermatitis comparative trial Isotretinoin 10 mg alternate days Group ISO. Patient opinion, investigator, and QoL
Group X: Topical anti-seborrheic topical assessments improved in both groups.
treatment
Sebaceous hyperpla- A case study N¼1 Low dose isotretinoin-dose not 3 month FU:
sia and sebaceous specified substantial improvement clinically and histologically
adenomas
Familial sebaceous A case study N¼2 0.2 mg/kg per day, a cumulative dose Case 1: no recurrence at 2 year FU
hyperplasia of 41 mg/kg (case 1) and 64 mg/kg Case 2: 1-month Rx with 0.3 mg/kg reduced to 0.5 mg/kg
(case 2), respectively for 9 months:
Outcome: No recurrence for 19 months
Cyclosporine-induced A case study N¼1 (1) Daily oral isotretinoin 20 mg for 2 (1) Near-complete remission, No SE.
sebaceous months: Two months after discontinuing, a few new lesions started
hyperplasia which resulted in to develop
(2) Oral isotretinoin 20 mg was (2) The lesions cleared without recurrence for 9 months.
restarted for 2 months.
(continued)
Table 1. Continued
Study
McDonald et al. 2011 (23)
Scarring alopecia
Marquis et al. (11)
Tietze et al. (50)
Part 3: Non-melanoma skin cancer prophylaxis, keratinization disorders, and miscellaneous
Non-melanoma skin cancer prophylaxis
Gahalut et al. (53)
Skroza et al. (17)
Tauber et al. (18)
Nijsten and Stern (54)
Levine et al. (45)
Moon et al. (63)
Indication Aim Patient number Dose Findings
Cyclosporine-induced A case series N¼2 Patient one: Patient one: almost complete clearance at 3 months
sebaceous (0.14 mg/kg) daily for 3 months, then SE: minor chelitis
hyperplasia maintained on this dose daily Patient two: almost complete clearance within 1 week,
Patient two: 0.29 mg/kg/day, then almost complete resolution at 4 months
maintained on this dose daily SE: nil
No change in graft function in either patient
Dissecting Cellulitis A case study N¼1 Isotretinoin 20 mg/day (0.27 mg/ 4-month FU: near complete remission
of scalp kg/day). 7-month phone follow up consultation: no further
recurrence
Folliculitis decalvans A retrospective N ¼ 28 Comparison of outcome between clin- Under treatment with isotretinoin, 90% of patients cured.
comparison study damycin and rifampicin, clarithromy- 10% did not improve significantly under therapy but went
cin, dapsone, and isotretinoin was into remission after the treatment was stopped.
analyzed.
48% treated with IST.
5% monotherapy
50% in combination-mainly dapsone.
0.2–0.5 mg/kg daily for 5–7 months.
After a stable emission, reduced by
10 mg 2 or 3 times a week for sev-
eral months before treatment
stopped.
Chronic plaque-type A randomized hospital- N ¼ 35 Control group: PUVA sol only Combination of IST with PUVAsol statistically more effect-
psoriasis vulgaris based study. Intervention group: ive than control group.
PUVAsol þ isotretinoin (0.5 mg/
kg/day)
SCC arising on an A case study N¼1 Isotretinoin 0.5 mg/kg/day for 5 months 70% reduction in size with no other relapses was
epidermoid observed during a 1-year follow-up.
cyst (15)
Unresectable A case study N¼1 Interferon (IFN)-a2a (3MUI subcutane- Clinical and radiological reassessment at 4 weeks of ther-
Perineal ously once a day) and isotretinoin apy showed a 50% tumor collapse
Cuniculatum (1 mg/kg per day) and Cidofovir
Carcinoma (5 mg/kg intravenously on weeks 0,
1, 3, and 5) however stopped due to
renal failure
Cutaneous squa- A cohort study N ¼ 135 Comparison of SCC and BCC incidence Retinoid use:
mous cell carcin- during years of substantial oral retin- 30% reduction in SCC incidence (P ¼ .002).
oma risk in oid use versus other years Post-adjustment for other factors associated with SCC risk,
patients with incidence of SCC: significantly decreased during years
psoriasis treated of substantial retinoid use.
with psor- Oral retinoid use and BCC incidence were not significantly
alen-UVA associated.
Skin cancer A randomized, double-blind, N ¼ 525 Group 1: oral retinol (25,000 units) Outcome measure:
prevention controlled trial. Group 2: isotretinoin (5–10 mg) Time to first new occurrence of BCC or cutaneous SCC.
Group 3: placebo supplementation No difference between groups.
daily for 3 years
Retinoids to prevent A RCT (1985–1990) N ¼ 719 25,000 IU retinol or 5–10 mg isotreti- No preventative effect of oral isotretinoin in the high risk
skin cancer noin versus placebo daily for 3 years candidates
JOURNAL OF DERMATOLOGICAL TREATMENT
in high risk candidates
(continued)
701
 702 E. FORBAT ET AL.

beneficial in sebaceous hyperplasia and sebaceous adenoma (7),

Macular hypomelanosis (9), eruptive syringomas (12), generalized lichen amyloidosis (13), lichen planus pigmentosus (49), lymphangioma circumscriptum (16), erythema dyschromicum perstans (6), sub-acute cutaneous

tive histiocytoma (28), prurigo pigmentosa (31), melanoma (43), vesiculous prurigo pigmentosa (32), follicular mucinosis (33), annular elastolytic giant cell granuloma (35), granuloma annulare (36), steatocystoma multi-
lupus erythematosus (21), chronic granulomatous disease (24), erythrokeratoderma variablilis (25), atrophoderma vermiculatum (26), synovitis, acne, pustulosis, hyperostosis, and osteitis syndrome (27), generalized erup-
1 month (FU): improvement of ischemia, softening of con-

8 month FU: keratoderma and ichthyosis lesions showed

partial improvement, no recurrence of pseudoainhum
cyclosporine-induced sebaceous hyperplasia in renal transplant
(15,23), and diffuse familial sebaceous hyperplasia (14).

Rosacea
Five studies reviewing the use of isotretinoin in rosacea have
shown promising results (20,22,40,41,52). Sbidian et al. carried out
Findings

an RCT among 156 patients with difficult to treat papulopustular

rosacea, comparing 0.25 mg/kg/day isotretinoin versus placebo,
striction, reduced pain.

with review at 4 months. Overall, the isotretinoin group demon-

strated higher absolute and relative reductions in the number of
lesions, as well as Skindex scores in comparison to the placebo
arm, suggesting quality of life (QoL) as well as clinical outcome
were better in the isotretinoin group (41). 58.3% of patients who
did attend follow-up had a relapse in their symptoms (41), similar
to Uslu et al. who found a 45% relapse at 11-month follow-up
(22). Rademaker demonstrated a 91% clearance of papulopustular
rosacea in patients treated with very low dose isotretinoin from
10 to 20 mg daily (40), and Gollnick et al. carried out a study
increased at 1 month to 0.35 mg/kg
Daily dose of 0.35 mg/kg body weight,

reviewing the use of various doses of isotretinoin (from 0.1 to

05 mg/kg of body weight) in conjunction with either doxycycline
or placebo; 0.3 mg/kg of isotretinoin to have the most effective
outcome in the treatment of rosacea (52).
Dose

Scarring alopecia
body weight

A recent case study demonstrated an excellent outcome of isotre-

tinoin 0.27 mg/kg/day in an 18-year-old male with dissecting cellu-
litis recalcitrant to multiple antibiotics, clotrimazole, and
betamethasone. At 4 months follow-up, there was near complete
remission, and via phone consultation (post-discontinuation of
Patient number

treatment) the patient did not report recurrence (11). In this case,
the authors postulated that isotretinoin reduced the overzealous
immune response and thus normalized the skin and follicular
N¼1

apparatus.
A retrospective study of 28 patients with folliculitis decalvans,
plex suppurativum (37), bilateral nipple hyperkeratosis (38), atrophoderma vermiculatum (39).

reviewed which treatment modalities had the best outcome using

either clindamycin and rifampicin, clarithromycin, dapsone or iso-
tretinoin. Isotretionin treatment was the most successful with 90%
of patients remaining in remission 2 years post-treatment cessa-
tion (50).
Aim

A case study

Viral warts
Isotretinoin has a good clinical outcome in the treatment of warts
(19,44). Al-Hamamy et al. demonstrated that 73.07% of warts
treated for 2 months with 0.5 mg/kg/day of oral isotretinoin
resolved, with 78.94% of the cohort found to have no recurrence
Vohwinkel syndrome
with ichthyosis

at 4 months (19). Another case study using isotretinoin in con-

Indication

junction with interferon had complete clearance at 3 months and

no recurrence at 1 year (34).

Cosmetic
Outcomes of photo-aging following treatment with systemic iso-
tretinoin remain mixed. Two studies have demonstrated that
Nico and Fernandes (10)

20 mg of isotretinoin daily, does not improve outcome in compari-

Keratinization disorders
Table 1. Continued

son to either topical retinoic acid or topical sunscreen, as assessed

by histology and quality of life (QoL) scores (42,48). Whereas one
Miscellaneous

case series demonstrated a statistically significant increase in colla-

gen fibers, post-treatment with either 10 or 20 mg isotretinoin
Study

three times per week for 3 months, with overall skin improvement
as a result (29). Interestingly, the use of isotretinoin has

dichotomous outcomes in Fordyce spots in patients with associ-
ated acne, with some showing improvement in Fordyce spots,
and others not (59).
Non-melanoma skin cancer (NMSC) prophylaxis
Immunosuppressed patients, for example organ transplant recipi-
ents, are at higher risk of NMSC. Articles often state that retinoids
have chemoprotective effects, however robust literature is lacking.
A Cochrane review of ten trials (N ¼ 7229) carried out in 2007
found that two trials within this review demonstrated evidence
that isotretinoin could either cause increased adverse effects, or
increase the risk of squamous cell carcinoma (SCC) in comparison
to placebo (60). However, they also stated that due to the small
number of trials and inconsistent results that they were unable to
declare that these results were reliable.
A randomized, double-blind, controlled trial compared the time
to first new occurrence of either a basal cell carcinoma (BCC) or
cutaneous SCC in 525 patients treated with either oral retinol
(25,000 units), 5–10 mg of oral isotretinoin, or a placebo over the
course of 3 years. They found no significant difference between
the groups, and no overall skin cancer prevention (45).
Skroza et al. reviewed the treatment of isotretinoin 0.5 mg/kg/
day for 5 months to a SCC on top of an epidermoid cyst. They
found a 70% reduction in the size with no further relapses at 1
year post-treatment (17).
Interestingly a cohort study of 135 patient comparing SCC and
BCC incidence during years of oral retinoid treatment compared
with non-treatment years in patients with psoriasis treated with
PUVA, found there to be a significant (p ¼ .002) 30% reduction in
SCC with retinoid use. However, retinoid use did not affect the
incidence of BCC (54). Moon et al. carried out the SKICAP-AK trial
which randomized patients with at least ten actinic keratoses and
up to two previous skin cancers to either placebo or 25,000 IU of
systemic retinol (precursor of retinoic acid) and found that retinol
is beneficial in reducing the incidence of first SCC but had no
effect on BCCs. They then carried out the SKICAP-SCC/BCC trial for
high risk patients (who had had at least 4 skin cancers previously)
and randomized these patients to treatment with either retinol or
oral isotretinoin at a dose of 5–10 mg daily or placebo, found no
benefit in this cohort (46,61). Interestingly, Clouser et al. re-
reviewed the statistics of the above studies in 2010, and declared
that in fact retinol could increase the risk of SCC in patients dur-
ing the first quartile or retinol dose. They also re-confirmed that
isotretinoin did not cause any significant reduction in outcome of
SCC or BCC (62).
Miscellaneous
Other conditions for which it has been suggested that isotretinoin
is beneficial, include: Vohwinkel syndrome with ichthyosis (10),
lichen amyloidosis (13), lymphangioma circumscriptum (16), ery-
thema dyschromicum (6), squamous cell carcinoma on epidermoid
cyst (17), unresectable perineal cuniculatum carcinoma (18),
chronic granulomatous disease (24), erythrokeratoderma variablilis
(25), atrophoderma vermiculatum (26,39), synovitis/hyperostosis/
osteitis syndrome and acne (27), prurigo pigmentosa (31), vesicu-
lous prurigo (32), follicular mucinosis (33), granuloma annulare
(36), steatocystoma multiplex suppurativum (37), and nipple
hyperkeratosis (38). Case studies have also been published which
show evidence for benefit of isotretinoin in lichen planus (49),
psoriasis (30,51,53), cutaneous lupus (21), and eruptive histocy-
toma (28). Most reports declared that although isotretinoin had
proved helpful, the authors were not sure on its mechanism of
JOURNAL OF DERMATOLOGICAL TREATMENT 703
action in those conditions. Those that did, felt isotretinoin’s mech-
anism of action were: anti-inflammatory (49), anti-angiogenic (16),
immunomodulatory (6), sebosuppressive (33), and anti-neoplas-
tic (43).
Refer Table 1 for an overview of these studies.
Conclusion
Isotretinoin, if used within the correct cohort, with appropriate
pretreatment counseling regarding side-effects, is a well-tolerated
medication with potential as either an adjunctive treatment or a
second line agent in those with disease recalcitrant to first line
therapy. To date, there has been interest demonstrated in isotreti-
noin use beyond the treatment of acne, however the majority of
studies presented are only case studies or small retrospective
reviews. Large RCTs are required to validate the possibility of iso-
tretinoin as an inexpensive drug to treat a multitude of other dis-
orders within dermatology, including most importantly, the use of
isotretinoin in NMSC which at present has contrasting outcomes.
Disclosure statement
The authors report no conflicts of interest.
References
1. IsotretinoinjDermNet New Zealand [Internet]. [cited 2017
Sep 9]. Available from: https://www.dermnetnz.org/topics/
isotretinoin/
2. Melnik BC. Apoptosis may explain the pharmacological
mode of action and adverse effects of isotretinoin, including
teratogenicity. Acta Derm Venerol. 2017;97:173–181.
3. Isotretinoin – DrugBank [Internet]. [cited 2017 Nov 9].
Available from: https://www.drugbank.ca/drugs/DB00982
4. Accutane was approved in May, 1982 with a pregnancy cat-
egory X [Internet]. [cited 2018 Jan 17]. Available from:
https://www.fda.gov/ohrms/dockets/ac/04/briefing/4017B1-
02%20%20AC%20Intro%20Review%20-Section%20A%20
Tab1.htm
5. Layton AM, Dreno B, Gollnick HPM, et al. A review of the
European Directive for prescribing systemic isotretinoin for
acne vulgaris. J Eur Acad Dermatol Venereol. 2006;20:
773–776.
6. Wang F, Zhao Y-K, Wang Z, et al. Erythema dyschromicum
perstans response to isotretinoin. JAMA Dermatol.
2016;152:841–842.
7. Gupta V, Mridha AR, Sharma VK. Sebaceous hyperplasia and
sebaceous adenomas presenting as leonine facies and
improving with oral isotretinoin. Clin Exp Dermatol.
2016;41:923–924.
8. Huang CM, Kirchhof MG. A new perspective on isotretinoin
treatment of hidradenitis suppurativa: a retrospective chart
review of patient outcomes. Dermatology. 2017;233:
120–125.
9. Damevska K, Pollozhani N, Neloska L, Duma S. Unsuccessful
treatment of progressive macular hypomelanosis with oral
isotretinoin. Dermatol Ther. 2017;30.
10. Nico MMS, Fernandes JD. Low-dose isotretinoin prevents
digital amputation in loricrin keratoderma (Vohwinkel syn-
drome with ichthyosis). J Dtsch Dermatol Ges J Ger Soc
Dermatol. 2017;15:665–667.
704 E. FORBAT ET AL.
11. Marquis K, Christensen L-C, Rajpara A. Dissecting cellulitis of
the scalp with excellent response to isotretinoin. Pediatr
Dermatol. 2017;34:e210–e211.
12. Papageorgiou M, Theodosiou G, Mandekou-Lefaki I. Eruptive
syringomas: unresponsiveness to oral isotretinoin. Int J
Dermatol. 2017;56:e38–e39.
13. Atacan D, Ergin C, Çelik G, et al. Oral isotretinoin: a new
treatment alternative for generalized lichen amyloidosis.
Australas J Dermatol. 2016;57:246–247.
14. Liu Y-CS, Cheng Y-P, Liu C-I, et al. Presenile diffuse familial
sebaceous hyperplasia successfully treated with low-dose
isotretinoin: a report of two cases and review of the pub-
lished work. J Dermatol. 2016;43:1205–1208.
15. Jung HY, Kim M, Cho BK, et al. A case of cyclosporine-
induced sebaceous hyperplasia in a renal transplant patient
successfully treated with isotretinoin. Ann Dermatol.
2016;28:271–272.
16. Ayhan E. Lymphangioma circumscriptum: good clinical
response to isotretinoin therapy. Pediatr Dermatol. 2016;33:
e208–e209.
17. Skroza N, Proietti I, Tolino E, et al. Isotretinoin for the treat-
ment of squamous cell carcinoma arising on an epidermoid
cyst. Dermatol Ther. 2014;27:94–96.
18. Tauber M, Monsel G, Bonnecarr
ere L, et al. Unresectable
perineal cuniculatum carcinoma: partial remission using sys-
temic isotretinoin and interferon-a2a therapy. Acta Derm
Venereol. 2014;94:721–722.
19. Al-Hamamy HR, Salman HA, Abdulsattar NA. Treatment of
plane warts with a low-dose oral isotretinoin. ISRN
Dermatol. 2012;2012:163929.
20. Rallis E, Korfitis C. Isotretinoin for the treatment of granu-
lomatous rosacea: case report and review of the literature.
J Cutan Med Surg. 2012;16:438–441.
21. D’Erme AM, Milanesi N, Difonzo EM, et al. Treatment of
refractory subacute cutaneous lupus erythematosus with
oral isotretinoin: a valid therapeutic option. Dermatol Ther.
2012;25:281–282.
22. Uslu M, Şavk E, Karaman G, et al. Rosacea treatment with
intermediate-dose isotretinoin: follow-up with erythema and
sebum measurements. Acta Derm Venerol. 2012;92:73–77.
23. McDonald SK, Goh MS, Chong AH. Successful treatment of
cyclosporine-induced sebaceous hyperplasia with oral isotre-
tinoin in two renal transplant recipients. Australas J
Dermatol. 2011;52:227–230.
24. Spillane AP, Hivnor CM. Isotretinoin use in a case of chronic
granulomatous disease. Pediatr Dermatol. 2009;26:756–758.
25. Singh N, Thappa DM. Erythrokeratoderma variabilis respond-
ing to low-dose isotretinoin. Pediatr Dermatol. 2010;27:
111–113.
26. Apalla Z, Karakatsanis G, Papageorgiou M, et al. A case of
atrophoderma vermiculatum responding to systemic isotreti-
noin. J Dermatol Case Rep. 2009;3:62–63.
27. Galadari H, Bishop AG, Venna SS, et al. Synovitis, acne, pus-
tulosis, hyperostosis, and osteitis syndrome treated with a
combination of isotretinoin and pamidronate. J Am Acad
Dermatol. 2009;61:123–125.
28. Kwinter J, DeKoven J. Generalized eruptive histiocytoma
treated with isotretinoin. J Cutan Med Surg. 2009;13:
146–150.
29. Rabello-Fonseca RM, Azulay DR, Luiz RR, et al. Oral isotreti-
noin in photoaging: clinical and histopathological evidence
of efficacy of an off-label indication. J Eur Acad Dermatol
Venereol. 2009;23:115–123.
30. Al-Shobaili H, Al-Khenaizan S. Childhood generalized pustu-
lar psoriasis: successful treatment with isotretinoin. Pediatr
Dermatol. 2007;24:563–564.
31. Akoglu G, Boztepe G, Karaduman A. Prurigo pigmentosa
successfully treated with low-dose isotretinoin. Dermatology.
2006;213:331–333.
32. Requena Caballero C, Nagore E, Sanmartın O, et al.
Vesiculous prurigo pigmentosa in a 13-year-old girl: good
response to isotretinoin. J Eur Acad Dermatol Venerol.
2005;19:474–476.
33. Arca E, Ko €se O, Taştan HB, et al. Follicular mucinosis
responding to isotretinoin treatment. J Dermatolog Treat.
2004;15:391–395.
34. Yildirim M, Inaloz HS, Baysal V, et al. A case of condyloma
acuminatum treated successfully with low-dose isotretinoin
and interferon. Int J Clin Pract. 2004;58:889–891.
35. Basak PY, Icke I, Akkaya VB, et al. Lack of response to isotre-
tinoin in annular elastolytic giant cell granuloma. J
Dermatol. 2004;31:678–681.
36. Young HS, Coulson IH. Granuloma annulare following wax-
ing induced pseudofolliculitis-resolution with isotretinoin.
Clin Exp Dermatol. 2000;25:274–276.
37. Apaydin R, Bilen N, Bayramg€ urler D, et al. Steatocystoma
multiplex suppurativum: oral isotretinoin treatment com-
bined with cryotherapy. Australas J Dermatol. 2000;
41:98–100.
38. Toros P, Onder M, G€ urer MA. Bilateral nipple hyperkeratosis
treated successfully with topical isotretinoin. Australas J
Dermatol. 1999;40:220–222.
39. Weightman W. A case of atrophoderma vermiculatum
responding to isotretinoin. Clin Exp Dermatol. 1998;
23:89–91.
40. Rademaker M. Very low-dose isotretinoin in mild to moder-
ate papulopustular rosacea; a retrospective review of 52
patients. Australas J Dermatol. 2018;59:26–30.
41. Sbidian E, Vicaut E, Chidiack H, et al. A randomized-con-
trolled trial of oral low-dose isotretinoin for difficult-to-treat
papulopustular rosacea. J Invest Dermatol. 2016;136:
1124–1129.
42. Bagatin E, Parada MOB, Miot HA, et al. A randomized and
controlled trial about the use of oral isotretinoin for photo-
aging. Int J Dermatol. 2010;49:207–214.
43. Richtig E, Soyer HP, Posch M, et al. Prospective, randomized,
multicenter, double-blind placebo-controlled trial comparing
adjuvant interferon alfa and isotretinoin with interferon alfa
alone in stage IIA and IIB melanoma: European Cooperative
Adjuvant Melanoma Treatment Study Group. J Clin Oncol.
2005;23:8655–8663.
44. Georgala S, Katoulis AC, Georgala C, et al. Oral isotretinoin
in the treatment of recalcitrant condylomata acuminata of
the cervix: a randomised placebo controlled trial. Sex
Transm Infect. 2004;80:216–218.
45. Levine N, Moon TE, Cartmel B, et al. Trial of retinol and iso-
tretinoin in skin cancer prevention: a randomized, double-
blind, controlled trial. Southwest Skin Cancer Prevention
Study Group. Cancer Epidemiol Biomarkers Prev.
1997;6:957–961.
46. Moon TE, Levine N, Cartmel B, et al. Design and recruitment
for retinoid skin cancer prevention (SKICAP) trials. The
Southwest Skin Cancer Prevention Study Group. Cancer
Epidemiol Biomarkers Prev. 1995;4:661–669.
47. de Souza Le~ao Kamamoto C, Sanudo A, Hassun KM, et al.
Low-dose oral isotretinoin for moderate to severe seborrhea

and seborrheic dermatitis: a randomized comparative trial.
Int J Dermatol. 2017;56:80–85.
48. Bagatin E, Guadanhim LRS, Enokihara MMSS, et al. Low-dose
oral isotretinoin versus topical retinoic acid for photoaging:
a randomized, comparative study. Int J Dermatol.
2014;53:114–122.
49. Muthu SK, Narang T, Saikia UN, et al. Low-dose oral isotreti-
noin therapy in lichen planus pigmentosus: an open-label
non-randomized prospective pilot study. Int J Dermatol.
2016;55:1048–1054.
50. Tietze JK, Heppt MV, von Preuszen A, et al. Oral isotretinoin
as the most effective treatment in folliculitis decalvans: a
retrospective comparison of different treatment regimens in
28 patients. J Eur Acad Dermatol Venereol. 2015;29:
1816–1821.
51. Mortazavi H, Khezri S, Hosseini H, et al. A single blind
randomized clinical study: the efficacy of isotretinoin plus
narrow band ultraviolet B in the treatment of psoriasis vul-
garis. Photodermatol Photoimmunol Photomed. 2011;27:
159–161.
52. Gollnick H, Blume-Peytavi U, Szabo  EL, et al. Systemic isotre-
tinoin in the treatment of rosacea – doxycycline- and pla-
cebo-controlled, randomized clinical study. J Dtsch Dermatol
Ges J Ger Soc Dermatol. 2010;8:505–515.
53. Gahalaut P, Soodan PS, Mishra N, et al. Clinical efficacy
of psoralen þ sunlight vs. combination of isotretinoin and
psoralen þ sunlight for the treatment of chronic plaque-
type psoriasis vulgaris: a randomized hospital-based
study. Photodermatol Photoimmunol Photomed. 2014;30:
294–301.
JOURNAL OF DERMATOLOGICAL TREATMENT 705
54. Nijsten TEC, Stern RS. Oral retinoid use reduces cutaneous
squamous cell carcinoma risk in patients with psoriasis
treated with psoralen-UVA: a nested cohort study. J Am
Acad Dermatol. 2003;49:644–650.
55. Excellence N-TNI for H and C. BNF: British National
Formulary – NICE [Internet]. [cited 2018 Jan 7]. Available
from: https://bnf.nice.org.uk/drug/isotretinoin.html
56. Boer J, Nazary M. Long-term results of acitretin therapy for
hidradenitis suppurativa. Is acne inversa also a misnomer?
Br J Dermatol. 2011;164:170–175.
57. Soria A, Canoui-Poitrine F, Wolkenstein P, et al. Absence of
efficacy of oral isotretinoin in hidradenitis suppurativa: a
retrospective study based on patients’ outcome assessment.
Dermatology. 2009;218:134–135.
58. Boer J. Are there indications for isotretinoin treatment of
hidradenitis suppurativa? Dermatology. 2017;233:111–112.
59. Mutizwa MM, Berk DR. Dichotomous long-term response to
isotretinoin in two patients with fordyce spots. Pediatr
Dermatol. 2014;31:73–75.
60. Bath-Hextall F, Leonardi-Bee J, Somchand N, et al.
Interventions for preventing non-melanoma skin cancers in
high-risk groups. Cochrane Database Syst Rev.
2007;(4):CD005414.
61. Moon TE, Levine N, Cartmel B, et al. Retinoids in prevention
of skin cancer. Cancer Lett. 1997;114:203–205.
62. Clouser MC, Roe DJ, Foote JA, et al. Dose response of retinol
and isotretinoin in the prevention of nonmelanoma skin
cancer recurrence. Nutr Cancer. 2010;62:1058–1066.
63. PubMed entry [Internet]. [cited 2018 Jan 8]. Available from:
http://www.ncbi.nlm.nih.gov/pubmed/8547834