DOI: 10.1111/jdv.

15813 JEADV

REVIEW ARTICLE

A systematic review of treatments for pityriasis lichenoides

F. Bellinato,* M. Maurelli, P. Gisondi, G. Girolomoni
Section of Dermatology and Venereology, Department of Medicine, University of Verona, Verona, Italy
*Correspondence: F. Bellinato. E-mail: francesco.bellinato@gmail.com

Abstract
Pityriasis lichenoides (PL) represents a spectrum of inflammatory skin diseases comprising pityriasis lichenoides et vario-
liformis acuta (PLEVA) and pityriasis lichenoides chronica (PLC). This study aimed to provide a summary of effective
treatments for PL. A systematic review was performed according to PRISMA guidelines for studies investigating PL
treatment including ≥3 subjects and published in English between 1 January 1970 and 15 April 2019. A total of 441
papers were screened, and 37 original manuscripts meeting the inclusion and exclusion criteria were found, including 12
case series, 18 reviews, four prospective studies, two comparative studies and a single randomized controlled study. In
most studies, ultraviolet (UV) phototherapy (narrow-band UVB, broadband UVB, UVA1 or PUVA) was used. Clearance
rates with the different modalities are hardly comparable between different studies, ranging approximately between 70%
and 100%. Narrow-band UVB showed an efficacy similar to PUVA as such as the combination of UVA and UVB vs.
PUVA. Oral erythromycin showed clearance rates ranging between 66% and 83%, whereas methotrexate up to 100%
but in small and dated studies. Evidence for other treatments is scarce. There is a lack of high level of evidence studies
on PL treatment. The interpretation of the results is biased by the possible auto-resolution of the disease, the sample
heterogeneity between children and adults and the short follow-up period of the studies. Only some studies investigated
how results were durable after cessation of therapy. Quality of life and the impact of treatment were never assessed.
According to the results of this review, we suggest narrow-band UVB phototherapy as first-line treatment. Oral ery-
thromycin with or without topical corticosteroids and low-dose methotrexate as second-line therapies. High-powered
studies and randomized controlled trials are needed to establish the optimal treatment for PL.
Received: 13 May 2019; Accepted: 8 July 2019

Conflicts of interest
None.

Funding source
None.

Introduction develop a centrally loosely adherent micaceous scale. Lesions

Pityriasis lichenoides (PL) comprises a spectrum of inflamma-
tory skin diseases which includes pityriasis lichenoides et
varioliformis acuta (PLEVA), febrile ulceronecrotic Mucha-
Habermann disease (FUMHD) and pityriasis lichenoides chron-
ica (PLC). PLEVA generally presents as an acute-to-subacute
polymorphous skin eruption of erythematous macules that
evolve into papules with micaceous scale free at the periphery.
Lesions may undergo haemorrhagic necrosis. In most cases,
lesions are distributed symmetrically on the trunk, buttocks and
proximal extremities. Varioliform scars and post-inflammatory
hyper- and hypopigmentation may result. Symptoms include
burning and pruritus. FUMHD presents with a rapid progres-
sion of necrotic papules to large coalescent ulcers with necrotic
crusts, haemorrhagic bullae and pustules. FUMHD is character-
ized by laboratory abnormalities and systemic manifestations.
PLC presents with erythematous-brownish papules which
often leave a hypopigmentated macule. PLC is usually asymp-
tomatic and follows a relapsing course with long periods of
remission. The descriptive terms acute and chronic refer to the
characteristics of the individual lesions and not to the course of
the disease. Individual patients may show intermediate or mixed
lesions.1 Epidemiology studies on PL are scarce. About 20% of
PL cases occur in the paediatric age and children are more likely
to show an unremitting course, frequent dyspigmentation and
poorer response to conventional treatment modalities.2 The
pathophysiology of PL is unclear. There are three major etio-
pathogenic hypotheses: (i) an inflammatory reaction triggered
by infectious agents or drugs (ii) an inflammatory response sec-
ondary to a T-cell dyscrasia and (iii) an immune complex-medi-
ated hypersensitivity vasculitis.3 Cell-mediated immune
mechanisms may be relevant in the development of the epider-
mal and vascular damage.4 This systematic literature review

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2 Bellinato et al.
aimed to provide a summary of effective treatments for PL
according to the best evidence available from published studies.
Methods
Search strategy
The present study was performed according to Preferred Report-
ing Items for Systematic Reviews and Meta-Analyses (PRISMA)
guidelines.5 Electronic searches were performed on PubMedâ
and Scopusâ database using ‘pityriasis AND lichenoides’ as
search terms.
Selection criteria
Original articles regarding PL treatments published between 1
January 1970 and 15 April 2019 were included. Eligible studies
comprised trials or studies of adult and/or children with a clini-
cal and/or histopathological diagnosis of PL (PLEVA and/or
PLC). Studies assessing any intervention were included, such as
topical treatments (corticosteroids and calcineurin inhibitors),
systemic agents (antibiotics and immunosuppressants) and pho-
totherapy. Exclusion criteria were as follows: articles written in a
language other than English, articles not reporting a clinical out-
come, meta-analyses, single case reports and case series describ-
ing <3 patients. The primary outcome was the therapeutic
efficacy, labelled as complete response (>90% improvement in
skin lesions), partial response (50–90% improvement) or no
response (<50% improvement).
Data extraction
Two investigators (FB, MM) independently extracted data by
using an extraction form. A third author (GG) was consulted to
resolve any disagreements. Articles were screened by title and
abstract and those deemed relevant were reviewed in full text
and selected or rejected based on the inclusion and exclusion cri-
teria. Data for the following items were extracted: study design,
patient characteristics (number of patients, age and sex, type of
PL), treatments received and results for outcome examined.
Evaluation of risk of bias
For randomized controlled trial (RCT), the risk bias was assessed
using the Cochrane Risk of Bias tool.6 For comparative studies,
the following items were considered for evaluation of risk of
bias: selection bias, performance bias, attrition bias, detection
bias and reporting bias. For case series and retrospective reviews,
definition of a precise diagnosis, inclusion and exclusion criteria,
outcomes, description of modalities of treatment, report of nat-
ural course of disease and observer bias were considered.
Results
A total of 441 references were identified through electronic data-
base searches and were screened by title and abstract. After
exclusion of duplicate and irrelevant references, a total of 167
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articles were deemed relevant and were reviewed in full text and
selected or rejected based on the exclusion criteria. All articles
were screened according to the scheme presented in Fig. 1. A
total of 37 original reports meeting the inclusion and exclusion
criteria were analysed, including 12 case series, 18 retrospective
reviews, four prospective studies, two comparative studies and a
single RCT with a sample of 15 patients. Among the 37 articles
included in the review, three concerned PLEVA, 10 PLC and
24 PL, comprising both PLEVA, PLC and overlap forms.
Tables 1–3 summarize the studies included in the analysis. Five
additional studies not responding the inclusion/exclusion crite-
ria were included, because they were considered relevant as
investigating different treatments useful as possible third-line
therapies.
Topical treatments
Topical corticosteroids Topical corticosteroids (TCS) are often
employed as the first-line therapy in clinical practice to alleviate
inflammation and pruritus. No RCT has compared topical corti-
costeroids with other treatments and some authors did not find
TCS to alter the course of the disease when used in monother-
apy.4 Longley et al.7 reported three cases of a chronic course
PLEVA in children treated with topical steroids without appar-
ent effect. Koh et al.8 reported three children with PLC-treated
topical corticosteroids. The median duration of disease before
presentation was 5–6 months. Patients were treated with a mean
duration treatment of 25 weeks without efficacy: one defaulted
follow-up and two required treatment with other modalities.
Gritiyarangsan et al.9 carried out a comparative study on 30
patients with PL treated with different modalities. The mean
Articles identified through PubMed®
and SCOPUS® database
(n = 441)
Articles excluded
(n = 274)
Articles deemed relevant
(n = 167)
Articles excluded
(n = 130)
Articles included in the systematic
review, (n = 37)
• 24 articles on PL (PLEVA/PLC)
• 10 articles on PLC
• 3 articles on PLEVA
Figure 1 Literature review screening scheme for articles included
in the systematic review of treatments for pityriasis lichenoides.
© 2019 European Academy of Dermatology and Venereology
Treatments for pityriasis lichenoides 3

Table 1 Summary of studies on the treatment of pityriasis lichenoides et varioliformis acuta (PLEVA)

References Type of Patients, Age (range, Sex Diagnosis Treatment Outcome

publication n median), years
Cornelison Case series 6 15–33 years, 3 male, PLEVA Methotrexate 7.5–20 CR in all the patients
et al. (1972)25 26 years 3 female mg per os weekly
Longley Case series 5 3–11 years, 4 male, PLEVA 3 patients with TCS NR with TCS
et al. (1987)7 7 years 1 female
Nguyen Van Retrospective 15 1–68 years, 10 male, PLEVA 8 patients with ‘Good response’
et al. (2019)16 review 22 years 5 female erythromycin
(or other macrolide)

CR, complete response; NR, no response; PR, partial response.

Table 2 Summary of studies on the treatment of pityriasis lichenoides chronica (PLC)

References Type of Patients, Age (range, Sex Diagnosis Treatment Outcome

publication n median), years
Takada Case series 15 7–45 years 6 male, PLC Heliotherapy PR in all the patients
et al. (1977)34 9 female
LeVine (1983)35 Case series 11 4–59 years, 3 male, PLC BB UVB (mean total CR in all the patients
29 years 8 female dose: 388 mJ/cm2)
Nassef and Retrospective 8 Not specified Not PLC Pyrimethamine and CR in 5 out 8 patients
Hammam review specified trisulfapyrimidine
(1997)31 (treating toxoplasmosis)
Risulo Case series 8 28–65 years, 3 male, PLC Oral bromelain CR in all the patients
et al. (2007)32 44 years 5 female
Ersoy-Evans Retrospective 18 3–16 years, 14 male, PLC 12 patients with BB UVB, 83% response with BB UVB
et al. (2008)37 review 9.5 years 4 female 5 NB UVB, 1 PUVA 100% response UVB, NR
with PUVA
Ersoy-Evans Retrospective 25 12–60 years, 14 male, PLC NB UVB phototherapy 48% CR, 44% PR
et al. (2009)40 review 34 years 11 female (mean total dose: 15 J/cm2)
Alajlan (2016)15 Case series 3 25–45 years, 2 male, PLC Minocycline 100% CR with minocycline
26 years 1 female (100 mg twice a day)
Fernandez- Prospective 8 18–69 years, 3 male, PLC NB UVB phototherapy 88% CR
Guarino study 44 years 5 female (mean total dose: 17 J/cm2)
et al. (2017)41
Cuellar Barboza Retrospective 19 1–45 years, 8 male, PLC 11 patients with NB UVB, 3 with 4 patients with CR with NB
et al. (2018)10 study 15 years 11 female oral erythromycin and TCS UVB, 7 with PR with NB
UVB; 100% PR with oral
erythromycin and TCS
Le Huu Prospective 29 3–75, 11 male, PLC NB UVB phototherapy 83% CR
et al. (2019)42 study 25 years 18 female (mean total dose: 9.8 J/cm2)

CR, complete response; NR, no response; PR, partial response.

duration of the symptoms prior to treatment was 9 months.
Eight patients with PL were treated with applications of topical
0.02–0.1% triamcinolone cream twice daily. Two patients had
complete remission in 1 month, two partial response and four
no response. Wahie et al.2 reported 16 children and 18 adults
with PL treated with topical corticosteroids (most commonly
clobetasol butyrate 0.05% for children and betamethasone valer-
ate 0.1% for adults). The mean duration of complaint prior to
consultation was 6 months in children and 24 months in adults.
A 50% of complete or partial clearance in each group was found.
Cuellar-Barboza et al.10 carried out a retrospective study on 19
patients with PL treated with different modalities. Five patients
with PLC were treated with class I topical corticosteroids for
4 months with complete response only in one patient and partial
response in three.
Topical calcineurin inhibitors Data are scarce and limited to
case reports. Simon et al.11 treated only two paediatric patients
affected by PLEVA and not responding to topical corticosteroids
or UVB phototherapy with tacrolimus 0.03% ointment twice
daily. A significant improvement was obtained within 4–6 weeks
and complete clearance in the other 3 months. Mallipeddi
et al.12 treated a patient with twice daily topical tacrolimus oint-
ment 0.1% with partial response in 4 weeks. Asahina et al.13

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Table 3 Summary of studies on the treatment of pityriasis lichenoides (PL), including pityriasis lichenoides et varioliformis acuta (PLEVA), pityriasis lichenoides chronica (PLC)
and overlap forms

References Type of Patients, Age (range, median), Sex Diagnosis Treatment Outcome

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publication n
Zlatkov and Retrospective 11 Not reported Not reported PL Pyrimethamine 50 mg daily for 5 days 3 CR, 2 PR
Andreev (1972)30 review (two cycles)
Piamphongsant Case series 13 11–54 years, 20 years 3 male, 10 female PL Tetracycline 2 g daily 5 CR, 7 PR, 1 NR
(1974)14
Lynch and Saied Case series 3 25–72 years, 32 years 1 male, 2 female PL (1 overlap, Methotrexate 25 mg IM or orally weekly CR in all the patients
(1979)26 2 PLC)
Boelen et al. Case series 5 22–65 years, 48 years 3 male, 2 female 3 PLEVA, 2 PLC 4 patients treated with PUVA (mean total CR in all the patients
(1982)47 dose: 34–316.5 J/cm2), 1 with UVA and
UVB phototherapy
Powell and Muller Case series 3 27–53 years, 27 years 3 female 2 PLEVA, 1 PLC PUVA (average total dose: 189–370.5 J/ Complete response with mild
(1984)48 cm2) recurrence
Truhan et al. Retrospective 22 2–15 years, 9 years 16 male, 6 female 14 PLEVA, 8 PLC 15 patients treated with oral erythromycin 11 (87%) CR, 2 PR, 2 NR
(1986)18 review (15–50 mg/kg/day)
Gritiyarangsan Comparative 30 2–25 years, 13 years 9 male, 21 female PL 8 patients with PUVA, 8 patients with 87% response with PUVA,
et al. (1987)9 study TCS (0.02–0.1% triamcinolone cream 86% response with TCS and
twice daily), 14 patients with TCS and tetracycline, 50% response
tetracycline 1–2 g daily with TCS
Gelmetti et al. Retrospective 89 8 months–14 years, 54 male, 35 female PL 12 patients with oral erythromycin (20– PR with erythromycin; UVB
(1990)17 review 11 years 40 mg/kg/day), most of the patients with alleviated symptoms
UVB phototherapy
Tay et al. (1996)36 Retrospective 5 6–12 years, 10 years 3 male, 2 female 3 PLEVA, 2 PLC BB UVB phototherapy (mean total dose: CR in all the patients
review 388 mJ/cm2)
Romanı et al. Retrospective 22 3–15 years, 9 years 10 female, 12 male 6 PLEVA, 16 PLC 8 patients with erythromycin (30–50 mg/ 70% response with
(1998)19 review kg/day) alone or with PUVA and/or TCS erythromycin
Pinton et al. (2002)49 Case series 8 20–58 years, 39 years 5 male, 3 female 3 PLEVA, 5 PLC UVA1 phototherapy (mean total dose: 6 (75%) CR, 2 PR
1125 J/cm2)
Boralevi et al. Open trial 13 2–40 years, 11 years, 7 male, 6 female 4 PLEVA, 9 PLC 12 patients with acyclovir or valaciclovir 2 CR, 6 PR
(2003)29 (22 controls) vs. placebo
Pasic et al. (2003)38 Prospective 9 8–16 years, 12 years 3 male, 6 female 3 PLEVA, 6 PLC NB UVB phototherapy (mean total dose: 3 CR, 3 PR, 3 NR
review 6.50 J/cm2)
Pavlotsky et al. Retrospective 29 36 years, 30 years 12 male, 17 female PL BB UVB vs. NB UVB (mean total dose: 93% CR in both groups
(2006)39 review (mean age in BB 3.6 and 15 J/cm2 respectively)
UVB and NB
UVB treatment
patients respectively)
Ersoy-Evans Retrospective 124 6–180 months 70 male, 54 female 46 PLC, 71 99 patients with oral erythromycin (30– 61% CR and 6% PR with
et al. (2007)20 review PLEVA, 50 mg/kg/day) alone or with TCS, other erythromycin
7 overlap therapies: oral cephalexin, oral
amoxicillin-clavulanic acid, oral cefaclor,
oral tetracycline, oral azithromycin, UVB
phototherapy
Bellinato et al.

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Table 3 Continued

References Type of Patients, Age (range, median), Sex Diagnosis Treatment Outcome
publication n
Wahie et al. (2007)2 Retrospective 57 2–65 years, 34 years 30 male, 27 female PL 34 with TCS (clobetasone butyrate 50% response with topical
review 0.05% or betamethasone valerate 0.1%), steroids, 25% response with
8 with oral erythromycin (40–60 mg/kg/ oral erythromycin, 71–88%
day), 16 with BB UVB phototherapy response with UVB
(mean total dose: 6 J/cm2), 6 with NB phototherapy
UVB (mean total dose: 14 J/cm2)
Aydogan et al. Retrospective 31 11–76 years, 43 years 11 male, 20 female 23 PLEVA, 8 PLC NB UVB phototherapy (mean total dose: 22 (70%) CR, 8 (35%) PR
Treatments for pityriasis lichenoides

(2008)33 review 23–16 J/cm2)

Farnaghi et al. Randomized 15 16–50 years, 31 years 8 male, 7 female PL NB UVB vs. PUVA phototherapy 71% response with NB UVB,
(2011)45 controlled 88% response with PUVA
(no difference)
Hapa et al. (2012)21 Retrospective 24 2–14 years, 7 years 14 male, 10 female 6 PLEVA, 15 PLC, Oral erythromycin (30–50 mg/kg/day) 83% response
review 3 overlap
Brazzelli et al. Case series 5 7–15 years, 10 years 1 male, 4 female 2 PLEVA, 3 PLC NB UVB phototherapy (mean total dose: CR in all patients
(2013)46 21 J/cm2)
Koh et al. (2013)8 Retrospective 15 8–91 years, 49.5 years 10 male, 5 female 2 PLEVA, 13 PLC 5 patients with oral erythromycin 3 out 5 patients response
review (500 mg bid-tid), 3 patients with NB UVB with erythromycin, 2 CR and
phototherapy, oral doxycycline, TCS, 1 PR with NB UVB, no
response with TCS
Park et al. (2013)44 Retrospective 70 2–80 years, 41 years 39 male, 31 female 24 PLEVA, 46 PLC NB UVB phototherapy (mean total dose: 92% CR with NB UVB, 80%
review 5.9 J/cm2), NB UVB phototherapy and CR with NB UVB and
systemic therapy (antibiotics not systemic therapy, 69% CR
specified) or systemic therapy alone with systemic therapy
Macias et al. Retrospective 13 23–83 years, 40 years 9 male, 4 female 2 PLEVA, 11 PLC 5 patients with UVA and UVB 2 patients with CR and 1 with
(2013)43 review phototherapy vs. 8 patients with PUVA PR with UVA and UVB
phototherapy phototherapy; 2 patients with
CR and 2 with PR with PUVA
phototherapy (no difference)
Zang (2018)51 Prospective 75 8 years, 38 years 40 male, 35 female 22 PLEVA, Phototherapy, heliotherapy, TCS, oral 13% CR with phototherapy,
study (mean age 50 PLC, 3 PL antibiotics 3% CR with heliotherapy,
in pediatric and adult 18% CR with TCS, 15% CR
patients respectively) with oral antibiotics; 47% PR
with phototherapy, 33% PR
with heliotherapy, 27% PR
with TCS, 25% PR with oral
antibiotics

CR, complete response; NR, no response; PR, partial response.

5

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6 Bellinato et al.
reported a 2-year-old boy with PL treated with TCS and topical
tacrolimus 0.03% ointment with better results than with TCS
alone.
Systemic agents
Antibiotics such as tetracycline, erythromycin and minocycline
have been used because infectious agents are possible trigger of
PL and because of their anti-inflammatory properties. Since
tetracyclines are contraindicated in children, erythromycin is
usually employed in this population.
Tetracyclines Piamphongsant14 reported a case series of 13
patients treated with oral tetracycline 2 g daily. Complete
remission occurred in five patients within 2–4 weeks, and
seven patients reported partial response and continued at the
dosage of 1 g daily for 4 weeks. Gritiyarangsan et al.9 carried
out a comparative study on 30 patients with PL treated with
different modalities. The mean duration of the symptoms
prior to treatment was 2 months. Fourteen patients were trea-
ted with oral tetracycline 1–2 g daily combined with topical
triamcinolone cream 0.02–0.1% applied twice daily. There was
one patient with complete remission, 11 with partial response
and two with no response. Wahie et al.2 reported four
patients with PL treated with minocycline 100 mg daily for
8 weeks. Complete clearance was observed in three patients
without relapses. Alajlan15 reported a case series of three
patients with PLC treated with minocycline. The mean dura-
tion of the symptoms prior to treatment ranged between
16 months and 3.5 years. 90%-complete response was
observed with minocycline 100 mg twice daily for 1–2 months
within 2 months. Two patients were previously treated with
topical corticosteroids and methotrexate and NB UVB pho-
totherapy.
8
Erythromycin Koh et al. carried out a retrospective study on
patients with a 5–6 month history of PL treated with different
modalities. Five patients with PLC were treated with oral ery-
thromycin 500 mg for 2–18 weeks. Lesions resolved in three
patients after a mean of 4.5 months, with no recurrence after
a mean of 7.3 months of follow-up. Cuellar-Barboza et al.10
reported three patients with PLC receiving a combination of
oral erythromycin 30–50 mg/kg/day for 3–4 cycles of 7–
10 days and class I topical corticosteroids with partial
response in all of them. Van et al.16 carried out a retrospective
review on 15 patients with PLEVA treated with different
modalities. Six patients were treated with erythromycin with
‘good response’ but did not mention the dosage of the drug
and if patients experienced relapses. Gelmetti et al.17 reported
‘moderate efficacy’ of 1- or 2-week courses of oral ery-
thromycin (20–40 mg/kg/day) on 12 children with PL (PLEVA
or PLC) with a disease duration ranging from 2 months to
10 years. Wahie et al.2 reported eight children with PL treated
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with oral erythromycin ethylsuccinate (40–60 mg/kg/day for
3–6 months). Clear or almost clear response was observed
only in two patients and one of them relapsed. Truhan et al.18
reported a retrospective study on 15 children with PL (11
PLEVA and four PLC) treated with oral erythromycin (15–
50 mg/kg/day). The duration of the disease varied from
6 weeks to 18 months at the time of presentation. Eleven
patients (73%) had a remission, usually within 2 months.
Two others showed partial improvement, and two were unim-
proved. One patient had a recurrence 5 months after the sus-
pension of the drug. Romanı et al.19 reported a retrospective
study on eight paediatric patients with PL (PLEVA or PLC)
treated with erythromycin (30–50 mg/kg/day) alone or in
combination with PUVA and/or topical corticosteroids. The
mean course of the disease was 1.6 months in patients with
PLEVA and 7.5 month in patients with PLC. Amelioration
and eventual disappearance of the lesions were observed in all
patients within 2–4 months, but relapses occurred in three
patients. Ersoy-Evans et al.20 reported a retrospective study on
99 paediatric patients with PL (PLEVA or PLC) treated with
oral erythromycin estolate or ethylsuccinate (30–50 mg/kg/
day) either alone or in combination with topical corticos-
teroids. The median duration was 20 months in patients with
PLC and 18 months in patients with PLEVA. The response
rate was 66.6% with a median response time of 2 months.
Hapa et al.21 reported a retrospective analysis on 24 children
with PL (six PLEVA, 15 PLC and three overlap) treated with
oral erythromycin 30–50 mg/kg/day for 1–4 months. The
median duration of the disease was 11 months. Response rate
was 83% in the third month. Relapse was observed in three
out 16 patients in follow-up.
Azithromycin There is only limited data in form of case reports.
Skinner et al.22 reported a 5-year-old boy with PLEVA who
failed on erythromycin and was treated with azithromycin
250 mg daily 5 days per week every other week for 12 weeks
with complete clearance. Di Costanzo et al.23 reported a 9-year-
old girl with PLEVA who failed erythromycin treated with oral
azithromycin (500 mg/day for three consecutive days every
other week) in association with topical tacrolimus 0.1% oint-
ment daily with efficacy. Ogrum et al.24 reported a complete and
persistent remission in a 13-year-old boy with an overlap PL
with 500 mg daily for three consecutive days every other week
for three cycles.
Other antibiotics Amoxicillin-clavulanic acid, cephalexin, cefa-
clor and ciprofloxacin were reported to be used for the treat-
ment of PL in some case reports. These antibiotics are generally
used after erythromycin failure or in the case of gastrointestinal
intolerance. Ersoy-Evans et al.20 reported 10 patients who failed
erythromycin and treated with a second antibiotic (usually
© 2019 European Academy of Dermatology and Venereology
Treatments for pityriasis lichenoides
cephalexin) with poor efficacy. Only two out of 10 patients
improved.
Methotrexate Systemic immunosuppressants like methotrex-
ate are generally reserved for recalcitrant or more severe cases
of PL or FUMHD. The mechanism responsible for the
improvement in PL lesions is unknown. Studies employing
methotrexate as treatment for PL include case reports and two
dated case series. Cornelison et al.25 reported clearing in six
patients with severe and long-lasting PLEVA treated with
methotrexate 7.5–20 mg per os weekly after 2–6 weeks. Most
of the induced remissions have lasted 2–4 weeks, but
responded again upon re-treatment. Lynch and Saied26
reported successful treatment of three cases of PL (one overlap
PL and two PLC) with methotrexate 25 mg weekly. Recur-
rence occurred in two cases after dose reduction.
Cyclosporine Excluding cyclosporine use in FUMHD, data are
scarce and limited to case reports. Lis-Swiez ty et al.27 reported a
rapid and persistent clearing in a 30-year-old woman with
PLEVA with cyclosporine A 3 mg/kg/day.
Pentoxifylline Data are limited to case reports. Sauer et al.28
used pentoxifylline 400 mg three times a day in two patients
previously treated with methotrexate, oral antibiotics and corti-
costeroids to treat the vasculitis aspect of PL with efficacy.
Acyclovir and valaciclovir Boralevi et al.29 carried out an
open trial on 12 patients with PL lasting from a mean of
6 months and treated with acyclovir or valaciclovir. All the
patients were screened for the presence of varicella zoster virus
(VZV) in lesional skin through polymerase chain reaction
analysis. VZV was found in eight cases (61.5%). Patients were
treated with aciclovir (patients aged <10 years) or valaciclovir
(patients aged >10 years). A significant improvement of the
cutaneous lesions was observed in eight cases (complete remis-
sion in two of them), a slight improvement in two cases and
no change in two cases. The response rate was not dependent
on VZV positivity.
Pyrimethamine and trisulfapyrimidine Zlatkov et al.30 carried
out a retrospective review on 11 patients with PL treated with
pyrimethamine 50 mg daily for 5 days, repeated after an inter-
val of 20 days. All the patients were tested for toxoplasmosis
by complement fixation test, intradermal test with toxoplas-
min and Sabin-Feldman tests. Six out of 11 were strongly pos-
itive. All six patients responded favourably: three reported
complete clearance and three partial clearance. The three toxo-
plasma-negative patients failed to improve. Nassef and Ham-
mam31 carried out a retrospective study on eight patients with
PLC and toxoplasmosis and observed the subsidence of PLC
lesions in five out of eight patients using pyrimethamine and
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7
trisulfapyrimidine within 2 months from the beginning of
therapy.
Bromelain Bromelain is a crude extract of pineapple containing
various proteinases with anti-inflammatory, fibrinolytic,
immunomodulatory and antiviral activity. Risulo et al.32
reported a retrospective review on eight patients with PLC trea-
ted for 3 months with oral bromelain (40 mg three times a day
for 1 month, 40 mg twice a day for 1 month and 40 mg/day for
1 month). The duration of the disease ranged between 15 and
34 months. All patients showed complete clinical recovery after
cessation of treatment, two patients experienced relapse 5–
6 months after suspension of therapy but responded to another
brief cycle of therapy.
Phototherapy
Ultraviolet (UV) light could modulate the skin immune
response perpetuating the lesions seen in PL.4 Phototherapy is in
general the most investigated successful therapy for PL, particu-
larly for PLC.33 In addition to heliotherapy, four phototherapy
modalities have been employed for the treatment of PL includ-
ing narrow-band UVB (NB UVB), broadband UVB (BB UVB),
UVA1 and PUVA phototherapy.
Heliotherapy Takada et al.34 reported a case series on 15
patients affected by PLC from several years and treated with sun-
light irradiation during the summer months. The daily exposure
was restricted to <2 h and gradually prolonged. Complete clear-
ing occurred in one patient, almost complete clearing in eight,
definite improvement in four and temporary clearing in two.
BB UVB phototherapy LeVine35 reported a case series on 11
patients affected by PLC and treated with BB UVB photother-
apy. The duration of the disease ranged from 10 months to
15 years. The spectral power distribution of the lamps extends
from 280 nm into the visible region with a broad peak at
313 nm. Disease cleared completely in all patients in an average
of 29 treatments (range 10–59), requiring an average UV dose of
388 mJ/cm2. In all patients, the axilla and the genitals were not
exposed to UV radiation and did not resolve until exposed. Tay
et al.36 reported a retrospective study on five children with
PLEVA treated with BB UVB phototherapy. All patients
responded with clearance of lesions, requiring an average of 26
treatments (range 22–33). The mean total clearance dose of UVB
was 4.2 J/cm2. Two patients relapsed after 7 and 9 months,
respectively. Ersoy-Evans et al.37 reported a retrospective review
on 18 paediatric patients with PLC treated with different pho-
totherapy modalities. Twelve children were treated with BB UVB
phototherapy. Response was observed in 83.3% of the patients
in an average of 18 sessions and with a median UVB total dose
of 11 J/cm2. Wahie et al.2 reported eight children with PL trea-
ted with BB UVB phototherapy with a median UVB total dose
© 2019 European Academy of Dermatology and Venereology
8 Bellinato et al.
of 6 J/cm2. Seven children were completed cleared or almost
cleared after treatment. Four subsequently relapsed within
3 months after cessation of treatment. By contrast, Gelmetti
et al.17 reported a retrospective study on 89 paediatric patients
with PL mainly treated with 4- to 8-week courses of BB UVB
phototherapy and observed alleviation of symptoms and control
of acute eruption but the course of the disease was not modified.
NB UVB phototherapy Pasic et al.38 carried out a prospective
study involving nine cases of PL (three PLEVA and six PLC)
treated with NB UVB and low potency topical corticosteroid.
NB UVB was administered 3–5 times per week and the median
total dose given was 6.50 J/cm2. The mean number of treatments
was 19. No improvement, partial clearance and complete clear-
ance was observed equally in each one-third of the patients.
Pavlotsky et al.39 reported a retrospective analysis of 29 patients
affected by PL and treated with BB UVB or NB UVB photother-
apy. The mean duration of disease prior to treatment was
31.7 months. The mean total cumulative dose administered was
3.6 and 15 J/cm2, respectively; the mean number of weeks of
treatments was 11 and 9 weeks, respectively. They found a com-
plete response in 93% of the patients of both groups and 27% of
the patients of both groups relapsed during follow-up. Ersoy-
Evans et al.40 reported a retrospective review of 25 patients
affected by PLC and treated with NB UVB phototherapy. The
mean duration of disease was 24 months. Complete response
and partial response were achieved in 48% and 44% of the
patients, respectively. Cumulative dose was 15 J/cm2 and the
median duration of sessions until response was 25. Relapse
occurred in 58% of the patients within a median of 9.5 months.
Fernandez-Guarino et al.41 carried out a prospective study on
eight patients with PLC whose disease showed no response to
topical therapy and lasting more than 6 weeks. Patients obtained
a complete response rate of 88% with a cumulative dose of
16.99 J/cm2 in a mean of 23 sessions. Relapse rate was 43% in
the first 6 months. Aydogan et al.33 conducted a retrospective
analysis in 31 patients with PL (23 PLEVA and eight PLC) trea-
ted with NB UVB. The mean duration of disease was 2 years in
patients with PLEVA and 0.7 years in patients with PLC. Com-
plete response was observed in 15 out of 23 patients (65.2%)
with PLEVA and in seven out of eight patients (87.5%) with
PLC with a cumulative dose of 23 and 15.6 J/cm2, respectively.
The mean number of treatments was 32.3 and 19, respectively.
Partial response was observed in eight patients (34.8%) with a
cumulative dose of 15.6 J/cm2. Relapse occurred in four patients
within 6 months. Wahie et al.2 reported eight adult patients
with PL treated with BB UVB phototherapy and six with NB
UVB phototherapy. The median total dose was 8 and 14 J/cm2,
respectively. The mean number of sessions was 18 and 17,
respectively. Overall, 10 completely cleared and only two of these
subsequently relapsed. Koh et al.8 reported three adults with
PLC who did not respond to erythromycin treated with NB
JEADV 2019
UVB phototherapy. Two had complete resolution after 2–
3 months of treatment and one had partial response after
1 month of treatment. Cuellar-Barboza et al.10 reported a retro-
spective study on 19 patients with PLC treated with different
modalities. Eleven patients with PLC were treated with NB UVB
with a total cumulative dose ranging between 2.4 and 103.1 J/
cm2. Complete and partial response was observed in four and
seven patients, respectively. The number of sessions was 91 and
28, respectively. One patient relapsed. Le Huu et al.42 reported a
retrospective study on 29 PLC patients treated with NB UVB
phototherapy. The mean disease duration was 39.9 months. A
complete response was seen in 24 patients (82.8%) with a mean
cumulative dose of 9.8 J/cm2 after a mean treatment period of
4.6 weeks. No relapses occurred in 24 complete response
patients within a mean period of 3 months after the last treat-
ment.
Macias et al.43 compared retrospectively in 13 patients with
PL (PLEVA and PLC) the clinical response of PUVA photother-
apy vs. UVA combined with UVB (UVA/UVB) phototherapy.
The median duration of disease was 14.6 months. The Authors
did not find significant difference between the two modalities.
The cumulative UVA dose was 84.4 and 26.1 and 3.62 J/cm2 for
UVA and UVB, respectively. Park et al.44 compared retrospec-
tively in 70 patients with PL (PLEVA and PLC) the efficacies of
NB UVB phototherapy, systemic therapy and the combination
of both. Patients with PLC had a longer disease duration than
those with PLEVA (16.4 months vs. 5.1 months, respectively). A
91.9% complete response rate was achieved in the NB UVB
group, whereas only 69.2% and 80.0% of patients achieved a
complete response in the systemic and combination treatment
groups, respectively, but these differences were not statistically
significant.
Farnaghi et al.45 carried out a RCT to compare the therapeu-
tic effects and the recurrence rates of NB UVB vs. PUVA pho-
totherapy in 15 patients affected by PLC. No significant
differences were found with a 71% and 88% response with NB
UVB and PUVA, respectively. The risk of bias was estimated to
be moderate. NB UVB phototherapy is a therapeutic modality
with a well-known efficacy and profile suitable also for paediatric
population. Brazzelli et al.46 treated five children (two PLEVA
and three PLC) with NB UVB phototherapy obtaining complete
remission after an average of 21 sessions without recurrence dur-
ing a 6-month follow-up. The average cumulative dose was 21 J/
cm2. Ersoy-Evans et al.37 reported 12 children with PL treated
with BB UVB phototherapy. Response was observed in 83.3%
with a total dose of 11 J/cm2. The same authors treated five chil-
dren with PL with NB UVB phototherapy with a total dose of 9–
301 J/cm2. All patients showed complete response, although no
details were given regarding follow-up.
PUVA phototherapy Gritiyarangsan et al.9 reported eight
patients with PL treated with PUVA phototherapy for 1–
© 2019 European Academy of Dermatology and Venereology
Treatments for pityriasis lichenoides 9

5 months (average 2 months). The duration of the symptoms
prior to treatment ranged between 2–6 months. Skin lesions of
patients cleared completely or were markedly reduced after an
average of 26 treatments (average dose of 68.80 J/cm2). Five
showed complete clearing; two, partial response; and one, no
response. PUVA was reported to be more effective than TCS or
the combination of oral tetracycline and TCS; however, the risk
of bias of this comparative study was estimated high. Boelen
et al.47 reported a case series on five patients with PL and treated
with PUVA or with a combination of UVA and UVB photother-
apy. The duration of the disease ranged from four to
102 months. Four out five patients (three with PLEVA and one
with PLC) were treated with PUVA phototherapy. The total dose
of UVA energy required to obtain remission was between 34.0
and 316.5 J/cm2. Long-term follow-up showed that two patients
had a recurrence at one and 23 months, though less severe than
before. Powell and Muller48 reported a case series on three
patients affected by PLEVA treated with PUVA therapy for a
period between 3 and 12 months on a C-3 schedule for a total
dose between 189 and 370.5 J/cm2. The duration of the disease
ranged from 7 to 24 months. The response was between 80%
and 100% and one patient reported a relapse.
UVA1 phototherapy Calzavara Pinton et al.49 reported a case
series on eight patients with PL treated with UVA1 photother-
apy. Patients received 60 J/cm2 UVA1 five times weekly until
remission. The mean cumulative dose was 1125 J/cm2. Six
patients showed complete recovery, two only partial. Relapse
was observed in four patients after a mean interval of 7 months.
Discussion
PL is an uncommon disease affecting children and adults. PL has
generally a chronic course with a variable duration ranging
between 1.6 months and several years.40 In a large paediatric
population study, the median duration of all forms of PL was
18.5 months, of PLC 20 months and of PLEVA 18 months.20 In
another large adult population study, the mean disease duration
was 5.1 month for PLEVA and 16.4 months for PLC.44
Although PL is generally a self-limiting disease, treatment is
required for controlling signs and symptoms, and the frequent
severe cosmetic disturbance. This systematic review investigated
treatments for PL according to the best evidence available from
published studies. A total of 37 original reports were analysed,
including 12 case series, 18 retrospective reviews, four prospec-
tive studies, two comparative studies and a single RCT with a
sample of 15 patients. Studies involved both children and adults.
Interestingly, outcomes of the studies involving paediatric
patients should be interpreted considering that in children PL is
more likely to show a poorer response to conventional treatment
modalities, compared with adults.2
Among the 37 articles included in the review, three concerned
PLEVA, 10 PLC and 24 PL, comprising both PLEVA, PLC and
overlap forms. Since PLEVA and PLC are generally considered
as two ends of a continuous spectrum, most of the studies
included patients affected by both diseases or overlap forms.
Even if TCS are frequently used as the first choice in the clini-
cal practice these drugs often provide partial response and unre-
sponsiveness is not infrequent. Evidence for the use of topical
calcineurin inhibitors (TCI) is still scarce. Oral tetracycline
shows often modest efficacy; in contrast, minocycline seems to
provide high percentage of complete clearance, but data are very
limited. Oral erythromycin provides a high percentage of
responses both in adults and in children, even if often not com-
plete. Cases refractory to erythromycin are rare. This antibiotic
could represent a suitable choice for paediatric cases. Response
to azithromycin, cyclosporin and pentoxifylline are limited to

PLEVA PL (PLEVA/PLC) PLC

Adults First-line:
Methotrexate (7.5-20 mg/w) Phototherapy Phototherapy
or (NB UVB, BB UVB,UVA1, PUVA, UVA/ (NB UVB, BB UVB, PUVA)
Oral erythromycin (500 mg bid-tid) UVB)
± ± ±
Topical corticosteroids Topical corticosteroids Topical corticosteroids
Second-line:
Oral erythromycin (500 mg bid-tid)
or
Methotrexate (7.5-20 mg/w)
±
Topical corticosteroids
Children Oral erythromycin (30-50 mg/kg/d) Oral erythromycin (30-50 mg/kg/d) Oral erythromycin (30-50 mg/kg/d)
or or
Phototherapy (NB UVB, BB UVB) Phototherapy (NB UVB, BB UVB)
± ± ±
Topical corticosteroids Topical corticosteroids Topical corticosteroids

Figure 2 Treatment algorithm for pityriasis lichenoides.

JEADV 2019 © 2019 European Academy of Dermatology and Venereology

10
few case reports. For the forms of PL of a proved reactive origin
to toxoplasmosis, the treatment of the underlying cause may be
an effective alternative. Antiviral therapy against varicella zoster
virus provided a high percentage of response in only one study
and was not related to the detection of the virus in skin samples.
Based on the beneficial role of sun exposure and heliotherapy,
UV phototherapy has been used for a long time and there are
many studies supporting its efficacy in PL. Different modalities
of UV therapy have been used including NB UVB, BB UVB,
UVA1 and PUVA phototherapy. Rates of response are high but
recurrences after cessation of phototherapy are common. PUVA
and UVA combined with UVB (UVA/UVB) phototherapy seem
to be equally effective; PUVA and NB UVB phototherapy; and
BB UVB and NB UVB phototherapy. In some studies, NB UVB
phototherapy was reported to induce a higher response in
patients with PLC compared with PLEVA (87.5% vs. 65.2%),33
however other studies did not find any differences.39 Therefore,
NB UVB appears the preferred phototherapy modality to use,
given its more favourable safety profile. In paediatric patients,
NB UVB phototherapy is usually used for a short period of time,
mitigating the potential carcinogenic risk of UVB exposure.
However, in chronic relapsing cases, in which a long course of
phototherapy is required, other modalities should be preferred
as first-line therapy.50 Only some studies compared treatment
responses of patients with PL in a long-term follow-up to assess
how are durable the results after the cessation of treatment. Zang
et al.51 reviewed treatment responses of 75 children with PL (50
PLC and 25 PLEVA) and conducted a long-term follow-up via
telephone interviews but did not report relapse rates for each
treatment. There were no differences in terms of response to
treatment between patients with PLC and PLEVA. By contrast,
82% patients with PLC and 19% with PLEVA had active disease
in the long term (22  35 months).
Our findings have several limitations. There is a lack of high
level of evidence studies on PL treatment. Most PL treatment
studies are anecdotal, case reports, case series and retrospective
studies. The interpretation of the results is biased by the frequent
auto-resolution of the disease, the sample heterogeneity between
adults and children and the short follow-up period of the stud-
ies. There are also possible selection bias and publication bias.
Finally, quality of life and the impact of treatment were never
assessed.
In conclusion, the current level of evidence on PL treatment is
limited. From the data available, UV phototherapy appears the
most effective treatment, and we suggest NB UVB phototherapy
as first-line therapy for PL, both PLC and PLEVA. Second-line
treatments could include oral erythromycin or methotrexate,
with or without TCS. Considering the few studies limited to
patients with the only form of PLEVA or PLC we suggest:
methotrexate or oral erythromycin for PLEVA; and UV pho-
totherapy for PLC. In children, we suggest oral erythromycin or
NB UVB phototherapy, preferring oral erythromycin for PLEVA
JEADV 2019
Bellinato et al.
and NB UVB phototherapy for PLC (Fig. 2). High-powered
studies and RCT are obviously needed to evaluate the efficacy of
treatments for PL.
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