Dermatology: Practical and Conceptual Original Article | Dermatol Pract Concept. 2023;13(2):e2023119 1 Clinicopathological Study of 307 Patients with Lichen Planus Actinicus and Pigmentosus Referred to Razi Skin Hospital From 2016 to 2021 Kambiz Kamyab1, Zahra Gholi1, Maryam Ghiasi2, Marzieh Pirzadeh1, Maryam Nasimi2 1 Department of Dermatopathology, Razi Hospital, Tehran University of Medical Sciences, Tehran, Iran 2 Babol university of Medical Sciences, Babol, Iran Key words: lichen planus actinicus, lichen planus pigmentosus, clinicopathology, vacuolar degeneration Citation: Kamyab K, Gholi Z, Ghiasi M, Pirzadeh M, Nasimi M. Clinicopathological Study of 307 Patients with Lichen Planus Actinicus and Pigmentosus Referred to Razi Skin Hospital from 2016 to 202. Dermatol Pract Concept. 2023;13(2):e2023119. DOI: https://doi. org/10.5826/dpc.1302a119 Accepted: November 30, 2022; Published: April 2023 Copyright: ©2023 Kamyab et al. This is an open-access article distributed under the terms of the Creative Commons Attribution- NonCommercial License (BY-NC-4.0), https://creativecommons.org/licenses/by-nc/4.0/, which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original authors and source are credited. Funding: None. Competing interests: None. Authorship: All authors have contributed significantly to this publication. Corresponding author: Maryam Nasimi, Department of Dermatology, Razi Hospital, Tehran University of Medical Sciences, Vahdate Eslami Street, Tehran, Iran. Zip code: 1199663911 Tel: 00982155618989, Nsm.maryam@gmail.com Introduction: The two less-known subtypes of lichen planus (LP) are lichen planus actinicus (LPA) and lichen planus pigmentosus (LPP), with the highest prevalence in the Middle East. Objectives: We aimed to evaluate the clinicopathological profile of these patients. Methods: Three hundred and seven cases including 184 LPA and 123 LPP patients were recruited from the registered pathology reports of Razi Skin Hospital of Tehran from April 2016 to March 2021. The clinical features and pathological reports were extracted and analyzed. Results: Among 307 patients, 117 (63.9%) in the LPA group and 88 (71.5%) in the LPP group were women. Duration of disease ranged from 1 month to 20 years and 1 month to 12 years in the LPA and LPP groups, respectively. Face (159 patients), limbs (68), and neck (23) were the most frequent sites of involvement in LPA patients, whereas face (60 patients), limbs (47), and trunk (42) were more commonly involved in the LPP patients. Pruritus and oral mucosal lesions were found with similar fre- quency in both groups. Pathological evaluation showed vacuolar degeneration of basal layer (100%), lymphocytes infiltration (97.3%), and melanin incontinence (58.2%) as the most frequent findings in LPA and vacuolar degeneration of basal layer (100%), lymphocytes infiltration (100%), and melanin incontinence (52/8%) as the most frequent findings in LPP cases. Conclusions: LPA and LPP were both more prevalent among women. Face was the most common site of involvement in both LPA and LPP. Vacuolar degeneration, lymphocyte infiltration, melanin inconti- nence, and hyperkeratosis were more common histological findings in this study. ABSTRACT 2 Original Article | Dermatol Pract Concept. 2023;13(2):e2023119 Introduction Lichen planus (LP) is a chronic, inflammatory, mucocutane- ous, and autoimmune disease that involves the skin and mu- cous membrane of the mouth and genitalia, scalp, and nails [1,2]. LP prevalence is unknown, but it is estimated that less than 1% of the population are affected by LP [2,3]. So far, about 13 subtypes of this disease have been re- ported including: classic, annular, hypertrophic, atrophic, ulcerative, bullous, pemphigoides, erythrodermic, inverse, linear, follicular, pigmentosus, and actinic [4]. LP actinic (LPA) is a photo-distributed type of LP which is often reported in darker-skinned people in the Middle East region and India. Lesions of LPA usually occur in the fore- head, face, neck, and extensor surfaces of the forearm and hands. The lesions usually flare up in warm seasons (spring and summer) and disappear in the winter. However, in rare cases, areas such as the trunk, legs, genitals, and feet that are not usually exposed to sunlight may also be involved. Contrary to the classic LP, the actinic type usually starts at younger age with a longer duration and more tendency for involvement of women with darker skin. Pigmentosus LP (LPP), which is more common in India and the Middle East, usually begins in the third and fourth decades of life and is slightly more common in women. Le- sions usually involve the face, neck, and, less commonly, flexor areas such as the axilla, groin, and infra-mammary folds. Similar to LPA, this type of LP is also more common in areas exposed to the sun [5,6]. Lesions of both LPP and LPA often occur in sun-exposed areas such as the face and neck, as well as presenting in the third to fifth decades of life [5-8]. Thus, these lesions can cause discomfort and anxiety for patients and significantly affect their professional, social, and family relationships. Therefore, prompt and timely diag- nosis and treatment of the disease can improve the quality of life of patients. Iran is located in the Middle East region; therefore, the prevalence of LPP and LPA is higher than in countries out- side the Middle East. However, no extensive study has been conducted in Iran to investigate the clinical features of these two types of diseases and to search for their indigenous differences compared to other countries. Discovering the common clinical signs and pathological features of LPA and LPP can help to accelerate the process of diagnosis, treat- ment, and improvement of the disease outcome, saving time and money. Objectives In this regard, we aimed to evaluate the clinicopathological features of patients with LPP and LPA who referred to Razi Hospital, Tehran, Iran, between April 2016 and March 2021. Methods This study is a cross-sectional descriptive retro-respective study including patients who referred to the outpatient clinic of Razi Hospital, and their pathology samples had been re- corded in the pathology department of Razi Hospital in Teh- ran, Iran, from April 2016 to March 2021. Among all patients, the cases whom LPA and LPP were reported as the differential diagnosis were evaluated and cases with final diagnosis of these two entities were selected for final evaluation. Cases that their diagnoses were post- poned to clinical follow-up and needed further evaluation were excluded from the study. Age, sex, clinical features, duration of symptoms, pres- ence of pruritus, location of lesions, and pathology registered data were extracted and recorded from the records of pa- tients. Pathology registered data were also extracted. Finally, 184 patients with LPA and 123 patients with LP were included in the study. Results Actinic Lichen Planus Among 184 LPA patients, 117 (63.9%) were women, and 67 (36.4%) were men and the female to male ratio was 1.74. The mean age of patients was 48.02±14.83, range of 8-102 years. The highest prevalence of LPP was among the age group of 50-59 years (29.35%). The interval between the on- set of symptoms and diagnosis varied from one month to 20 years, and the average interval was 23 months. In 44.25% of patients, it was less than one year, in 22.12% one to two years, and in 8% of patients more than 5 years (Table 1). Considering the site of involvement, 159 (86.4%) of pa- tients had facial lesions and face was the most common site of involvement in LPA. Among 159 patients with facial le- sions, the forehead, cheeks, nose were the most common sites of facial lesions, respectively. After the face, the limbs were the second most common site of involvement (68 out of 184 patients), most commonly on the dorsum of the hands, arms, forearms, and lower limbs. Followed by the face and limbs, the neck, trunk, ears, axilla, and groin were commonly in- volved, and in one patient, generalized lesions were recorded (Table 1 and Figure 1). Out of 184 patients, 7 had oral mucosal involvement and 25% of patients experienced pruritus (Table 1). Regarding the pathological features found in the skin bi- opsies of patients with LPA, we demonstrated that the most prevalent pathological features were vacuolar degeneration (100%), lymphocyte infiltration (97.3%), melanin inconti- nence (58.2%), hyperkeratosis (55.4%), and melanophage (42.9%), respectively. Among 179 skin biopsy slides that had lymphocytic infiltration, 4 types of infiltration were observed Original Article | Dermatol Pract Concept. 2023;13(2):e2023119 3 Table 1. Clinicopathological features of lichen planus. LPA (N = 184) LPP (N = 123) Gender Female 117 (63.59%) 88 (71.54%) Male 67 (36.41%) 35 (28.46%) Age Mean ± SD 48.02 ± 14.83 41.55 ± 14.23 Range 0-9 year 1 (0.5%) 2 (1.6%) 10-19 8 (4.3%) 5 (4.1%) 20-29 9 (4.9%) 15 (12.2%) 30-39 30 (16.3%) 35 (28.5%) 40-49 46 (25%) 31 (25.5%) 50-59 54 (29.3%) 20 (16.3%) 60-69 24 (13%) 13 (10.6%) 70-79 9 (4.9%) 2 (1.6%) 80-89 2 (1.1%) 0 90-99 0 0 100-110 1 (0.5%) 0 Duration Mean ± SD 23±36.47 21±31.66 Range <1year 50 (44.2%) 42 (50.6%) 1-2 25 (22.1%) 22(26.51%) 2-3 13 (11.5%) 3 (3.61%) 3-4 6 (5.3%) 4 (4.81%) 4-5 10 (8.8%) 2 (2.4%) 5< 9 (8%) 10 (12.05%) Pruritus 46 (25%) 30 (24.39%) Location Face 159 (86.4%) 60 (48.8%) Limbs 68 (37%) 47 (38.2%) Neck 23 (12.5%) 21 (17.1%) Trunk 11 (6%) 42 (34.1%) Scalp 4 (2.2%) 1 (0.8%) Ears and around 3 (1.6%) 3 (2.4%) Groin 1 (0.5%) 8 (2.4%) Axilla 2 (1.1%) 20 (16.3%) Generalized 1 (0.5%) 4 (3.3%) Mucosal involvement 7 (3.8%) 4 (3.3%) Histopathology Vacuolar degeneration 184(100%) 123(100%) Hyperkeratosis 102 (55.4%) 54 (43.9%) Lymphocyte infiltration 179 (97.3%) 123 (100%) Melanin incontinence 107 (58.2%) 65 (52.8%) Acanthosis 52 (28.3%) 38 (30.9%) Hypergranulosis 36 (19.6%) 14 (11.4%) Parakeratosis 22 (12%) 4 (3.3%) Infiltration of melanophages 79 (42.9%) 74 (60.2%) Civatte body 56 (30%) 40 (32.5%) Thinning or atrophy of the epidermis 54 (29.3 43 (35.5%) Infiltration type Band like 128 (71.5%) 95 (77.2%) Deep 33 (18.4%) 12 (9.8%) Perifollicular 46 (25.7%) 19 (15.4%) Perivascular 85 (47.5%) 72 (58.5%) LPA = lichen planus actinicus; LPP = lichen planus pigmentosus; SD = standard deviation. 4 Original Article | Dermatol Pract Concept. 2023;13(2):e2023119 of involvement and forehead was the most common site on the face. Following the face, limbs were the second common site, that 47 out of 123 (38.2%) patients were presented with limb lesions, mainly on the dorsum of the hands, arms, fore- arms, and lower limb. Out of 42 patients (34.1%) who had trunk lesions, distribution of lesions were back lesions (15), intermammary (4), inframammary (3) chest (5), abdominal (5), lumbar (2), and 1 case of flank and buttock lesions. In addition, only 7 patients with trunk involvement were male, and 35 were female (Table 1 and Figure 1). Regarding pathological findings, vacuolar degeneration (100%), lymphocyte infiltration (100%), melanophage in- filtration (60.2%), melanin incontinence (52.8%), hyper- keratosis (43.9%), thinning or atrophy of the epidermis (35.5%), civatte body (32.5%), acanthosis (30.9%), and hypergranulosis (11.4%) were the most common findings, respectively (Table 1). Of the 123 skin biopsy slides that had lymphocytic in- filtration, four types of infiltration were found, including band-like or superficial (77.2%), deep (9.8%), perifollicular (15.4%), and perivascular (58.5%) (Table 1). as follow: superficial or band-like (71.5%), deep (18.4%), perifollicular (25.7%), and perivascular (47.5%) (Table 1). Pigmented Lichen Planus Evaluating the clinical features of 123 patients with LPP, similar to LPA, LPP was more frequent in the female sex, 88  were women (71.5%) and 35 were men (28.4%). The mean age of patients with LPP was 41.55±14.23 years (range 6-77 years). The 53.66% of patients were aged 30-49 years. The interval between the onset of symptoms and diagnosis was ranging from one month to 12 years with the average interval of 21 months. In 50.6% of pa- tients, this interval was less than one year, in 26.51% one to two years, and in 12.05% of patients more than 5 years. Among 123 patients, 30 of them experienced itching at the time of referral or in the past. Mucosal involvement was seen in 4 of 123 patients (Table 1). Generally, the most common sites of lesions in LPP were: face, limbs, trunk, neck, axilla, and groin, respectively. Furthermore, 4 patients had generalized lesions. Sixty pa- tients (48.8%) had facial lesions as the most common site Figure 1. Clinical and histopathological features of lichen planus actinicus (LPA). (A,C) Clinical picture of LPA. (B,D) Photomicrograph of lichen planus actinicus showing hyperkeratosis, atrophy of epidermis, wedged shaped hypergranulosis, vacuolar degeneration, melanin incontinence, civatte bodies and perivascular lymphocyte infiltration. Original Article | Dermatol Pract Concept. 2023;13(2):e2023119 5 interval of 23 months. In 44.25% of patients, the period was less than one year. However, 8% of patients have had a course of more than 5 years, which is a significant number compared to previous studies. Dilaimy et al reported that minimal itching could ac- company LPA lesions only in the summer [11]. Similarly, M. Salman et al. demonstrated that itching was almost al- ways absent in LPA patients [12]. In our study, we found that out of 184 patients, 46 patients (25%) had pruritus. Therefore, the presence of pruritus cannot rule out the di- agnosis of LPA. In Salman et al study, out of 16 patients with LPA, 15 had facial lesions, 12 had involvement of the dorsum of the hands or the outer surface of the forearm, and 3 had in- volvement of the V area of the chest. Non-exposed areas and mucus membranes were not involved in these patients [12]. Similarly, our results demonstrated that the involvement of sun-exposed areas was predominant. Besides among patients with limb involvement, the dorsum of the hands, forearms and arms were the most affected sites, respectively. Oral mu- cosal involvement was also observed in 7 patients. An im- portant finding of our results that is worth to be mentioned was the involvement of axillary and groin regions which are not exposed to the sun. Conclusions To the best of our knowledge, our study described the clin- icopathological features of LPA and LPP patients in a large population for the first time. It has been investigated that women suffering from LPA outnumbered men suffering from LPA based on previous re- ports similar to our results [9-12]. Dostrovsky et al have shown that LPA was most com- mon in 21 to 31 years (39%) [9]. In the contrary, our results showed that although 90.2% of patients were over 30 years old, but the highest prevalence of LPA was in the age group of 50-59 years (29.35%). Studies reported the majority of LPA cases in young adults from second to forth decade of their lives from middle Eastern descent [13]. This difference could be attributed to the ethnic population and geographic difference [14]. According to Salman et al study, the interval between the onset of symptoms and LPA diagnosis in 81% of patients was one year or less [12]. The duration of LPA was reported one year in 74% of patients, two years in 11%, and more than two years in 13% of patients in Dostrovsky et al study [9]. In our study, this interval varied from one month to 20 years with an average Figure 2. Clinical and histopathological features of lichen planus pigmentosus (LPP). (A,C) Clinical picture of LPP. (B,D) Photomicro- graph of lichen planus pigmentosus showing epidermal thinning, hyperkeratosis, vacuolar degeneration of basal cell layer, basal cell layer pigmentation, and perivascular lymphocyte infiltration. 6 Original Article | Dermatol Pract Concept. 2023;13(2):e2023119 and 3.2% of patients, respectively [5]. Mendiratta et al. found that the most common sites of involvement were the head and neck, followed by the involvement of the upper back. The disease did not affect the mucous membranes, pal- mar and plantar surfaces [17]. In Al-Mutairi et al study, mu- cosal lesions were present in only one patient, and the nails, palmar and plantar surfaces were all intact [15]. In our study, face was the most common site of involve- ment (48.8%). Facial involvement was mainly on the fore- head, cheeks, and eyelids. Followed by the face, the limbs (38.2%), trunk (34.2%), neck (17%), axilla (16.3%), and groin (6.5%) were the most frequent involved parts, respec- tively. 4 patients (3.3%) had mucosal involvement. Similar to other studies, palmar and plantar surfaces were not affected in patients. The back was the most common site of lesions among trunk lesions. Regarding pathological findings, Al-Mutairi et al re- ported that band-like infiltration of lymphocytes was the most common form of lymphocyte infiltration pattern in bi- opsy samples of LPP patients (63%) [15]. In our study, vacuolar degeneration and lymphocyte infiltration were found in all samples. The most common lymphocyte infiltration pattern was superficial. Other pathological findings were macrophage infiltration, melanin incontinence, hyperkeratosis, thinning or atrophy of the epi- dermis, hypergranulosis, and parakeratosis. Our LPA cases had higher mean age. Prevalence of pruri- tus was 25% in LPA patients with 7 patients with oral muco- sal involvement which were considered absent or rare in some studies. In contrast to prior studies, lymphocyte infiltration was not all band-like and confined to the upper dermis, in many cases, they were patchy and involved reticular dermis. Hypergranulosis, which was considered a constant finding in some studies, was present in 19.6% of cases. Among LPP cases, a higher rate of trunk lesions was recorded compared to previous studies. Vacuolar degeneration, lymphocyte in- filtration, epidermal atrophy, and hyperkeratosis were also more prevalent in this study among LPP patients. Availability of Data and Materials: The datasets used and/ or analyzed during the current study are available from the corresponding author on reasonable request. References 1. Le Cleach L, Chosidow O. Clinical practice. Lichen planus. N Engl J Med. 2012;366(8):723-732. DOI: 10.1056/NE- JMcp1103641. PMID: 22356325. 2. [Usatine RP, Tinitigan M. Diagnosis and treatment of lichen pla- nus. Am Fam Physician. 2011;84(1):53-60. PMID: 21766756. 3. Parihar A, Sharma S, Bhattacharya SN, Singh UR. A clinico- pathological study of cutaneous lichen planus. J Dermatology Regarding pathological findings, in our study, vacuolar degeneration was observed in all samples, which is the main finding of diseases involving dermo-epidermal junction. The next finding was lymphocytic infiltration in 97.3% of cases. 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