A prospective study to find out epidemiological spectrum, Etio-clinico and histopathological correlation of cicatricial alopecia encountered in tertiary care centre of Western Rajasthan

Cicatricial alopecia is an enigmatic group of hair disorders in which follicular units are replaced by fibrous tissue, resulting in progressive and permanent scarring hair loss^1-4. It has always been a diagnostic and therapeutic challenge to the dermatologists^2,5. Historically, one of the first descriptions of type of cicatricial alopecia was given by Brocq in 1885 which was later known as Pseudopelade⁶. In 1888, Quinquaud described pustular folliculitis with scarring which is now known as Folliculitis decalvans⁷. Cicatricial alopecia is also classified according to a consensus-issued classification scheme based on the predominant cell type present: lymphocytic, neutrophilic, or mixed and hence histopathology has important role in the diagnostic evaluation⁸. It may result from a disease process affecting the hair follicles primarily or secondary to external disease process including trauma, burns, chemicals, chronic infections, systemic disease or malignancy^{7, 9}.

Various classification schemes exist in literature with distinction based on clinical features, age of onset and pathology using different terminologies^{5, 7- 9}. In 2001, NAHRS issued a working classification based on predominant type of inflammatory infiltrate so that uniformity can be achieved in terminologies thus allowing better correlation¹¹. The disorders were categorized in lymphocytic, neutrophilic, mixed and non-specific groups. Epidemiology of cicatricial alopecia is widely unknown with prevalence ranging from 3.2-7.3%^{1, 12-13}. Majority of the patients belong to primary cicatricial alopecia^{1-2, 12}. Females are affected 3-4 times more commonly than males¹¹. Most common causes of primary cicatricial alopecia include Discoid lupus erythematosus (30-35%), Pseudopelade (25-30%), lichen-planopilaris (20-25%), and folliculitis decalvans (10-15%) ^{1, 12-13}. Majority of cicatricial alopecias, differing clinical presentations which change over time and often overlap thus making accurate diagnosis challenging for both the clinician. Cicatricial alopecia is trichologic emergency as the resultant alopecia is often irreversible¹. A perfect diagnosis is usually reached with the help of clinico-pathological features, stigmata of other cutaneous disorder along with special investigations^1-3. Thus a scalp biopsy is warranted in all cases^{1, 7-8}.  For histopathological evaluation, minimum 4 mm biopsy sample from active site are required while, another sample is needed for direct immunofluorescence (DIF)⁸. The aim of this study was to find out epidemiological spectrum and to describe prospectively the histopathological outcomes of cicatricial alopecias & correlate with clinical diagnosis. Aditionally, on the basis of etiology it can be classify as primary and secondary cicatricial alopecia.

A prospective and clino-histopathologic evaluation of 84 consecutive patients of cicatricial alopecia attending the dermatology outdoor was performed who meet inclusion criteria. All patients with clinical evidence of cicatricial alopecia irrespective of age, sex and duration of the disease were enrolled in the study. The patients with prescence of thrombocytopenia (<50,000/mm3) or disorders of  coagulation, HIV or any immunodeficiency, Pregnancy and nursing women, predisposition to keloid formation and psychological problems were exclude from the study. After written consent, detailed history, clinical examination and the baseline investigations like complete blood count, ESR, KOH for fungus were done in each case and relevant investigations like ANA, culture for fungus and bacteria were performed when required. Based on history and clinical and laboratory finding, diagnosed as cicatricial alopecia. Then a punch biopsy 4-5 mm in size was done from the active advancing margin of latest alopecic patch to include both the scarred area and nearby clinically normal skin.  The biopsy was sent to pathological department for histopathological evaluation and compare to clinical diagnosis. In present study, the informed consent document and any subsequent modifications were reviewed and approved by the Institutional ethics committee (IEC).

In present study,  table -01 communicated that total 84 patients comprised of females 69.1% and  males 30.9%. The age at the onset of disease varies from 7 years to 59 years with a mean age of 27.57 years. Maximum numbers of cases were seen between the age group of 10-30 years. The cases were categorized into various groups i.e. Lymphocytic [mediated (DLE, LPP, PPB), Neutrophilic mediated (FD) and miscellaneous groups in accordance with NAHRS working classification for primary cicatricial alopecia. After final diagnosis there were 85.7% cases of lymphocyte mediated group and all the other groups showed equal frequency of 4.76%. According to table-02, the ratio of lymphocytic mediated versus all other: 6:1. In the lymphocyte mediated group maximum numbers of cases were found out to be of Lichen planopilaris (35.7%), DLE (31%), Pseudopelade (16.7%). The duration of the disease varied markedly ranging from as short as 15 days to 16 years, with a mean duration of 2.42 years.

Table No. 1: Age and Sex distribution of patients with cicatricial alopecia.   N=84

Clinical profile: - The present study highlighted that the most common characteristic was asymptomatic to erythematous plaques and hair loss patches in 88.1% cases. The most common presenting features of DLE (figure-1) present in >50% cases were itching, scaling, follicular plugging, hyperpigmentation, telangiectasia and atrophy & LPP presented with itching, tenderness, follicular erythema, hyperpigmentation and activity at margin (figure-2). All Pseudopelade cases and end stage disease presented with asymptomatic well defined atrophic patches. Patients of folliculitis decalvans (figure-3) presented with papules, pustules with crusting and few atrophic patche.  Pseudopelade (16.7%) presented with irregular, shiny and atrophic patches of alopecia with islands of normal hair (figure-4).

Table No. 2: Distribution of cases according to NAHRS working classification

Table No. 3: CLINICAL FINDINGS

Table No. 4: HISTOPATHOLOGICAL FIDINGS

Table No. 5: Correlation between clinical histopathological and final diagnosis. N=84

FIGURES: CLINICAL AND HISTO-PATHOLOGICAL

Fig 1- Scalp DLE, showing thin atrophic skin with white atrophic plaque with loss of follicular ostia.

Fig 2-Patch of LPP, scarred dyspigmentaion violaceous skin with few areas of loss of follicular ostia.

Fig 3-Folliculitis Decalvans showing scarred scalp with yellowish, crusted pustules at the periphery with matted and tufted hairs in the centre of plaque.

Fig 4 -Multifocal, skin-colored plaques of pseudopelade of Brocq with complete loss of follicular ostia and no signs of inflammation

Fig 5 -A case of lichen planopilaris. Hair follicle infiltrated by lymphocytes (seen in lower half of the image). H&E 40X

Fig 6 -Cicatricial alopecia. The image shows a vertical fibrotic band in the centre, with isolated Arrector pili muscle, without accompanying pilosebaceous units. H&E 40X

Fig 7 -scalp biopsy of cicatricial alopecia shows hair follicles in deep dermal-subcutis junction replaced by fibrovascular areas. H&E 40X

Histopathological findings:

Inflammatory infiltrate was composed of mainly lymphocytes in 90.5% (76) of total cases which included all the cases of DLE and LPP and 71.4% cases of Pseudopelade. Both the cases of folliculitis decalvans showed mixed inflammation composed mainly of neutrophils, lymphocytes and plasma cells. Mostly, 84.6% cases of DLE and 93.4% of cases of LPP lymphocytic infiltrate present at the dermo-epidermal junction surrounding the follicular infundibulum and isthmus. It was also seen in 71.4% cases of Pseudopelade and 2 cases each of folliculitis decalvans and fungal folliculitis. Deep follicular involvement was seen in 1 case each of FD but it was not found to be statistically significant (Table 4). By clinical examination the cases showed marked overlapping features. 18 cases of LPP could be correctly diagnosed on clinical examination where as 6 cases of LPP showed overlapping features with DLE and 6 presented with end stage features and resembled Pseudopelade clinically. DLE was diagnosed definitely by clinical examination in 12 cases whereas in rest all cases definite diagnosis was not possible as there were overlapping features with LPP. On clinical examination, Pseudopelade could be definitely diagnosed in majority of the cases. Only, 4 cases presenting within one year of onset showed some features of activity with mild erythema and clinically LPP was also kept as differential diagnosis. Folliculitis decalvans was diagnosed correctly in 2 cases when presented early with features of papules and pustules While, other 2 cases showed overlapping features with fungal folliculitis (Table 5). By histopathological examination, majority of cases (90.47%) were correctly diagnosed. Histopathology alone correctly diagnosed 86.6% cases of LPP and 84.6% cases of DLE. All the cases of Pseudopelade, folliculitis decalvans and fungal folliculitis were correctly diagnosed.   The histopathology shows all features of end stage scarring alopecia, with concentric perifollicullar fibrosis, no sebaceous glands, loss of follicular units and minimal residual inflammatory cell infiltrate (figure-5, 6, and 7).

There is paucity of data on cicatricial alopecia worldwide. Limited studies are available regarding comparative clinical, histopathological and immunological findings of cicatricial alopecia in past. Epidemiology of cicatricial alopecia is largely unknown with only two retrospective studies available worldwide with no study done so far in the Indian context. The aim of conducting this study was to evaluate the clinical characteristics, histopathological findings in patients with cicatricial alopecia in Western Rajasthan. In our study, there were 69% females and 31% males and this was in accordance with most of the studies in western literature ^{12, 13, 21, 23}. Whereas, in some studies, the male female ratio was comparatively high^12-13.  In terms of age group, cicatricial alopecia was reported in 10-30 years as compared to 31-40 years in most western studies ^{12-15, 19}. Only 5 children (11.9%) had cicatricial alopecia with female to male ratio of 1.5:1 similar to adults. In this context, few studies reported only 2-4% pediatrics cases ^{12-13, 15}. There is no study available from Indian subcontinent illustrating the epidemiology except a study on lichen planopilaris demonstrating that prevalence in children is more than west. We found that LPP contributed to 40% cases in children followed by 20% each of Pseudopelade, folliculitis decalvans and fungal folliculitis. We found that lymphocyte mediated group constituted 85.7% of all the cases after categorizing the cases into various groups according to NAHRS classification¹¹. This was slightly higher as compared to study by Whiting¹³ and Tan et al¹⁴ where this group comprised 77.1% and 80.3% cases respectively. In lymphocyte mediated group, maximum number of patients (35.7%) belonged to LPP. This was in accordance to study by Amato et al which concluded it as 33.3%¹⁵. This was unlike the observations in other studies by Tan et al¹³. This may be due to the fact that end stage LPP is categorized as secondary pseudopelade in these studies. In the present study DLE comprised 31% of total cases, which was in accordance with studies by Tan et al¹³ and Moure et al¹⁶ where they reported it as 33.9% and 37.2% respectively.

In present study, Pseudopelade comprised 16.7% of total cases while, various studies communicated that number of cases of Pseudopelade varies from 10% to 33%. ^{11-14, 22, 25}.

Folliculitis decalvans was diagnosed in 4.76% cases. This was in accordance with study by Moure et al where they reported Folliculitis decalvans in 6.7% cases¹⁶. In present study, all the case of Pseudopelade, majority of patients of LPP and 84.6% cases of DLE presented with patches and plaques. The present finding was supported by various studies. ^13,14,22,25.

Histopathological findings

Hyperkeratosis was present in 84.6% cases of DLE which is in accordance with studies by Moure et al¹⁶, Fabbri et al²⁶. Two-third of cases with LPP showed hyperkeratosis which is consistent with previous studies.^{20, 23-26}. It was also seen in 71.4% cases of Pseudopelade. There is no statistical significance between various groups and HK.

In our study epidermal atrophy was noticed in 69.2% cases of DLE which was consistent with observations of Fabbri et al²⁶ and Annessi et al²⁷.  Only, 26.7% cases of LPP reported epidermal atrophy while, in the biopsy in Pseudopelade group 28.2% cases had epidermal atrophy which is in accordance with previous studies^{13, 14}.

Additionally, all the cases of DLE, LPP and majority of cases of Pseudopelade highlighted lymphocytic infiltrate. Whereas, Neutrophilic and mixed infiltrate was seen in folliculitis decalvans.

Among the lymphocyte mediated group, 93.4% cases of LPP showed lichenoid infiltrate involving the isthmus and infundibulum only. One-fifth of cases showed band like infiltrate at dermo-epidermal junction. This is consistent with findings of Moure et al¹⁶, Annessi et al²⁷ and Tandon et al²². In cases of DLE, variably dense lymphocytic infiltrate mixed with plasma cells in 15.4% was seen around superficial part of follicle in 84.6% which is in context with previous studies^{13, 14, 20-22}.  Only 15.4% cases of DLE showed complete loss of hair follicle with diffuse dense fibrosis. Furthermore, in 71.4% cases of Pseudopelade there was mild lymphocytic infiltrate around isthmus and infundibulum. While, some studies reported that it varies from 0-64%^21-27. This could be contributed to varying duration of presentation of patients with minimal inflammation in end stages. Moreover, all the cases of folliculitis decalvans showed neutrophilic infiltrate with mixed inflammation in one case. This has been reported in previous study by Whiting¹³, Tan et al¹⁴ and Otberg et al²⁸.

Correlation of clinical, histological and final diagnosis

By clinical examination the cases showed marked overlapping features. Only 18 cases of LPP were correctly diagnosed on clinical examination whereas, 6 cases of LPP showed overlapping features with DLE and 6 presented with end stage features and resembled Psedopelade clinically. DLE was diagnosed definitely by clinical examination in 12 cases while,  in rest all cases definite diagnosis was not possible as there was overlapping features with LPP. Additionally, Pseudopelade could be definitely diagnosed in majority of the cases on the basis of clinical examination. Four cases presenting within one year of onset showed some features of activity with mild erythema and clinically LPP was also kept as differential diagnosis.

Moreover, Folliculitis decalvans was diagnosed correctly in two cases when presented early with features of papules and pustules. Other two cases showed overlapping features with LPP as the patient presented with atrophic patches with papules. This is consistent with findings of Otberg et al²⁸and Powell et al²⁹. Furthermore, in mostly cases (90.5%) accurate diagnosis was done by histopathological examination. On histopathology basis, correctly diagnosed cases of LPP and DLE were 86.6% and 84.6% respectively. This is consistent with findings of Trachsler and Trueb³⁰ and Moure et al¹⁶. All the cases of Pseudopelade, folliculitis decalvans and fungal folliculitis were correctly diagnosed, in this context, Trachsler and Trueb³⁰ also reported that the accuracy to diagnosis was 97% on histopathology ground.

Limitation: The present study was conducted on small same size with lack of dermatoscopy and trichoscopic findings, lack of immunoflourence study and other special stains.

The primary scarring alopecia is diagnostic challenge, which is faced by the clinician and pathologist. Overlapping clinical features are there because of heterogeneous group. Cicatricial alopecia is a trichological emergency, hence required meticulous management to prevent further complications and follicular destruction. The study, recommended that scalp biopsy should be done in each case from an active lesion. Furthermore, multiple sections should be analyzed in each case. The histological features vary drastically with stage of the disease hence, should be supplemented with special stains PAS, Methyl Trichrome and VVG. DIF has both supplemental and diagnostic role in Lymphocytic group especially in histologically suspected cases. Moreover, for a prompt and accurate diagnosis, combined clinico-pathological and immunologic approaches are needed.

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