Management of Primary Cicatricial Alopecias: Options for Treatment

M.J. Harries; R.D. Sinclair; S. MacDonald-Hull; D.A. Whiting; C.E.M. Griffiths; R. Paus

Disclosures

The British Journal of Dermatology. 2008;159(1):1-22. 

In This Article

Lymphocytic Group

CCLE is a relatively common dermatosis characterized by well-demarcated, erythematous and scaly plaques on sun-exposed sites. The plaques slowly enlarge, revealing atrophic scarring with variable degrees of telangiectasia and dyspigmentation. Less than 10% of patients who present with CCLE will progress to develop systemic disease.[19] A thorough examination along with measurement of full blood count, urinalysis, antinuclear antibodies and extractable nuclear antigens is mandatory in all affected individuals.

Scalp involvement is common in adults with CCLE.[20] Symptoms may include pruritus, burning or scalp tenderness. Inflammatory activity is most pronounced centrally within the area of alopecia (Figure 2). Follicular plugging and adherent scale may be observed. Histopathological features include hyperkeratosis, follicular plugging and interface changes (vacuolar>lichenoid) with resulting basal layer damage. Periadnexal and perivascular lymphocytic infiltrates may be seen in both the superficial and deep dermis. A moderate amount of dermal mucin is usually present. Direct immunofluorescence may reveal a band-like deposition of immunoglobulins and complement at the dermoepidermal junction. The pathogenesis of CCLE is unknown but may represent an autoimmune reaction to an unknown trigger.[21]

Inflammatory activity most pronounced centrally within the area of alopecia (diagnosis = chronic cutaneous lupus erythematosus).

Treatment. Drugs for CCLE have been reviewed in a Cochrane systematic review;[22] two RCTs were identified as having sufficient quality for inclusion (see below).[23,24] As CCLE is often made worse by exposure to ultraviolet (UV) radiation, photoprotection with a hat or a broad-spectrum sunscreen should be used daily.[25,26]

First-line Treatment.

Potent topical corticosteroids (Level of evidence = A)

Intralesional triamcinolone acetonide (Level of evidence = C)

A 12-week crossover RCT (n = 58) demonstrated benefit for a potent topical corticosteroid cream (fluocinonide 0.05%) when compared with a weaker preparation (hydrocortisone 1%). Clinical response was scored on a five-point scale, ranging from deterioration of disease to clearance, assessed at a single test site.[23] A further controlled, but nonrandomized trial comparing fluocinolone 0.025% with vehicle showed benefit for the topical steroid, demonstrated by improvement in redness, scaling, induration and extent of disease.[27] Complete remission occurred in four of five patients with CCLE treated weekly with clobetasol propionate lotion under DuoDERM® occlusion.[28] Other studies also support the use of topical corticosteroids in CCLE.[29,30,31,32,33,34]

Weekly injections of intralesional triamcinolone acetonide (ILTAC; 10mgmL−1) demonstrated 'improvement' or clearance in 39 of 41 patients from two separate trials.[35,36] [In some papers outcome measures are not clearly defined. To make this clear to the reader we have recorded the reported outcome in quotation marks (e.g. 'improved'). Obviously caution is required when interpreting these studies.] A series of 40 patients found a 'good to excellent response' in 88% of patients when treated with ILTAC (3–4mgmL−1), with five patients experiencing complete disease control.[32] Whiting stated that ILTAC (10mgmL−1) injected every 4–6weeks 'may be the treatment of choice' for CCLE.[8] Others have also shown benefit for ILTAC.[37]

Callen found oral corticosteroids rarely effective in CCLE, with 22 of 25 patients treated showing a poor response.[32] Others have, however, demonstrated greater efficacy with oral steroids.[38,39,40] Oral corticosteroids are not commonly used as standard treatment in CCLE as long-term maintenance therapy with these agents is undesirable due to toxicity.

Second-line Treatment.

Antimalarials (Level of evidence = A)

Oral retinoids (Level of evidence = A)

An RCT of acetretin vs. hydroxychloroquine demonstrated overall clinical improvement, assessed by changes in erythema, induration and scale, in 13 of 28 (46%) treated with acitretin and 15 of 30 (50%) treated with hydroxychloroquine. No statistically significant difference in efficacy between the two treatments was demonstrated; however, side-effects were greater in the acitretin group.[24] In particular, acitretin can produce a dose-dependent telogen effluvium that is poorly tolerated by patients with existing hair loss. Another discouraging finding in this respect is that it has recently been shown that all-trans retinoic acid inhibits the growth of organ-cultured human scalp hair follicles and induces the expression of catagen-stimulating and potentially scar-promoting transforming growth factor-β in their dermal papilla.[41] Small studies and case series report benefit for retinoids, particularly in hypertrophic discoid lupus erythematosus (DLE); however, this form of lupus erythematosus is uncommon on the scalp.[42,43,44,45,46,47,48]

A controlled but nonrandomized trial of high-dose hydroxychloroquine (n = 24) vs. placebo (n = 25) demonstrated hydroxychloroquine to be more effective than placebo; however, outcome measures were not clearly defined.[49] Jewell and McCauliffe[50] also demonstrated benefit, defined as complete or partial reduction in size or number of lesions, for antimalarials in CCLE and also noted that smokers were less likely to respond to treatment than nonsmokers. A 'very good to excellent' result was reported in 24 of 34 (70%) patients with CCLE treated with hydroxychloroquine as monotherapy.[32] In cases unresponsive to single-agent antimalarial therapy, combination treatment with chloroquine and mepacrine may be beneficial.[51,52,53]

Third-line treatment.

Thalidomide (Level of evidence = B)

Topical immunomodulators (Level of evidence = A)

Oral vitamin E (Level of evidence = B)

Oral gold (Level of evidence = B)

Dapsone (Level of evidence = B)

Clofazimine (Level of evidence = B)

Most studies of thalidomide treatment in CCLE are in patients who had previously failed other treatment modalities. Forty-four of 60 patients treated with thalidomide (200mg twice daily) for 3–6months showed either complete regression or significant regression with some residual activity; however, a relapse rate of 71% was noted.[54] In a prospective open uncontrolled trial (n = 22) complete remission (=90–100% clearance) was observed in 12 patients, and considerable improvement (=70–80% clearance) in a further five patients.[55] Over 150 patients are reported in various trials and case series as benefiting from thalidomide in doses ranging from 50 to 300mg daily.[56,57,58,59,60,61,62,63,64,65,66,67,68,69]

Topical 1% pimecrolimus cream applied twice daily for 8weeks demonstrated improvement, assessed by a defined clinical severity score, in all patients treated in a small, open-label phase II study.[70] Other authors have also reported benefit with topical pimecrolimus.[71,72]

A small RCT (n = 4) [despite a good level of evidence rating, the small number of patients with CCLE in this study limits the conclusions that can be drawn; patient numbers are therefore recorded, where possible, throughout this review to highlight the problem] compared 0.1% tacrolimus ointment with 0.05% clobetasol propionate ointment in a 4-week bilateral comparison study. Improvement was recorded on a seven-point rating scale. No difference in outcome was demonstrated between the treatment groups.[73] Tacrolimus 0.1% ointment applied twice daily has been used with variable success.[74,75,76,77,78] Walker et al.[79] reported complete resolution of inflammation in two patients with 0.3% tacrolimus in clobetasol propionate ointment applied twice daily.

Vitamin E (tocopherol) 600–2000IU daily may be helpful in DLE.[80,81,82,83] Burgess and Pritchard reported 'improvement' in 24 of 25 patients;[84] Grubb[85] reported 'improvement' in 47 patients and Welsh also reported benefit.[86] However, others have been unable to reproduce these
findings.[87,88,89]

Gold (auranofin) at 3–9mg daily improved 19 of 23 patients, who had previously failed with topical steroids and antimalarials, in one multicentre open study. Clinical outcome was assessed by a three-point clinical scale.[90] A further study reported 'improvement' in three of eight patients.[91]

Thirty-three of 45 patients treated with clofazimine (100–300mg daily) were 'cured', with 45% remaining relapse free after 1–3years of follow-up.[92] Improvement, based on a clinical grading system, was seen in 17 of 26 patients in a prospective open trial.[93] Dupréet al.[94] observed 'remission' in all six patients treated, after 3months of therapy, and Krivanek and Paver[95] stated 'no patient failed to improve' without supplying patient details.

Dapsone (100mg daily) resulted in an 'excellent response' in 24% and 'some response' in a further 24% of 33 patients treated; in 52% no effect was observed.[96] Nine of 11 patients, after 6–16weeks of treatment, 'improved' in an open pilot study.[97] Others have also reported benefit with dapsone.[98]

Other.

Topical imiquimod (Level of evidence = E)[99,100]

Topical 5-fluorouracil (Level of evidence = C)[101]

Topical tazarotene (Level of evidence = E)[102]

Laser (Level of evidence = C) [103,104,105,106,107,108]

Sulfasalazine (Level of evidence = D) [109,110,111,112]

Interferon alfa (Level of evidence = C) [113,114,115,116]

Methotrexate (Level of evidence = D) [117,118,119,120]

Azathioprine (Level of evidence = E) [121,122,123]

Phenytoin (Level of evidence = B)[124]

Oral β-carotene (Level of evidence = E)[125]

Cryotherapy (Level of evidence = E) [126,127,128,129]

Suction blister grafts (Level of evidence = E)[130]

Cyclophosphamide (Level of evidence = D)[131]

Ultraviolet A1 (Level of evidence = E)[131]

Extracorporeal photopheresis (Level of evidence = E)[132,133]

Chimeric CD4 monoclonal antibodies (Level of evidence = E)[134]

Colchicine (Level of evidence = E)[135]

B12 injections (Level of evidence = C)[136,137]

Isoniazid (Level of evidence = E)[138]

Mycophenolate mofetil (Level of evidence = E)[139,140]

Chloramphenicol (Level of evidence = D)[141,142]

Biological therapies–infliximab/efalizumab (Level of evidence = C)[143,144]

Danazol (Level of evidence = E)[145,146]

Ciclosporin (?ineffective–Level of evidence = E) [147,148,149,150]

The above treatments have all been explored in CCLE. Limited evidence suggests that ciclosporin is ineffective in CCLE. See cited references for details.

LPP is regarded as a follicular variant of lichen planus (LP) based on histopathological and immunofluorescence findings.[151] Three forms of LPP are recognized: classic LPP, frontal fibrosing alopecia and Graham Little syndrome (GLS; discussed below). A further entity has recently been described where patients develop a progressive fibrosing alopecia confined to areas of androgenetic alopecia; this has been termed fibrosing alopecia in a pattern distribution (FAPD). Histological findings in early lesions of FAPD are identical to those of LPP. Interestingly, four patients in the original cohort (n = 19) responded to antiandrogens or finasteride, suggesting that the lichenoid tissue reaction might be pathologically related to events underlying androgenetic alopecia.[152]

Presenting symptoms in LPP include alopecia, increased hair shedding, pruritus, burning and tenderness. Perifollicular erythema and follicular hyperkeratosis are seen in affected, hair-bearing skin, and are most prominent at the edge of the alopecia (Figure 1). An expanding rim of activity develops, leaving a central zone of scarring. Multifocal patches, often with a central distribution, are common. Anagen hairs may be extracted from areas of active disease. LPP tends to occur in adults and is more common in women. LP on other parts of the skin may be apparent in up to 50% of cases at some point in the disease course.[151]

Histopathological features are similar to classic LP. A lichenoid interface dermatitis involving the upper follicle may be seen along with infundibular hyperkeratosis, hypergranulosis, basal layer destruction and cytoid bodies. Sebaceous glands are often atrophic or absent.

Treatment. Resolution of associated symptoms and the absence of visible inflammation do not automatically imply that hair loss has been arrested. Alopecia can progress insidiously over many years. The paucity of RCTs is partially explained by the difficulty investigators have in monitoring the efficacy of treatment, and in designing meaningful trial end-points. To be effective, any of the currently available treatments must be maintained in the medium to long term. While cutaneous LP is known to burn out over time, the same cannot be guaranteed for LPP.

First-line treatment.

Potent topical corticosteroids (Level of evidence = B)

Intralesional triamcinolone acetonide (Level of evidence = D)

A clinical trial of 30 patients treated with high-potency topical steroids for 12weeks demonstrated resolution of inflammation and halting of disease progression in 66%, with mild improvement seen in a further 20%. There was no response in 13%.[153] Mehregan et al.[151] reported a 70%'improvement' with potent topical corticosteroids in a series of 20 patients. A 'fair' treatment response, defined as 'unstable disease with minimal response to treatment', was reported in 13 of 24 (54%) patients with potent topical steroids; and a 'good' response, defined as 'stabilization of disease with greater than minimal response to treatment', in seven of 24 (29%).[154] Combination therapy of topical corticosteroids with oral antihistamines (cetirizine) has been reported as effective, with 13 of 14 patients responding to this treatment.[155] ILTAC demonstrated a 'fair' response (defined above) in 10 of 20 (50%) and 'good' response in eight of 20 (40%).[154] Newton et al.[156] reported benefit for ILTAC (3–5mgmL−1); however, Mehregan et al..[151] found ILTAC to be ineffective in all seven patients treated. Others have also reported benefit with ILTAC.[157]

Second-line treatment.

Oral corticosteroids (Level of evidence = D)

Oral ciclosporin (Level of evidence = C)

Topical ciclosporin (Level of evidence = C)

Oral tetracycline (Level of evidence = D)

Oral corticosteroids resulted in 'improvement' in nine of 11 (82%) patients. The dose was not specified and the relapse rate was 80% within 1year.[151] Oral corticosteroids are reported as particularly useful in rapidly progressive disease.[158,159]

A small prospective study of 13 patients treated with oral ciclosporin demonstrated complete resolution of disease activity in eight of 13 (53%) and a partial response in two of 13 (23%). The authors concluded that optimal treatment required a dose between 4 and 5mgkg−1 daily for 4–6months. Relapse rates were, however, high (60%) at 6months follow-up.[159] Three other patients improved within 3–5months with ciclosporin at 300mg daily.[160] Others have reported benefit with oral ciclosporin.[153]

An oily solution of ciclosporin (diluted in 1-methyl-2-pyrolidinone and ethylic acid; final conc. = 1.5%) was applied topically twice daily for 3months, then once daily for a further 3months. Complete remission was observed after 3–4months of treatment in 14 of 18 patients, with seven patients exhibiting sporadic regrowth of hairs.[161] One other patient is reported as benefiting from topical ciclosporin.[153] Oral tetracyclines produced improvement in 10 patients: 36% had a 'fair' response and 55% a 'good' response (defined above) to this treatment.[154]

Third-line treatment.

Oral retinoids (Level of evidence = C)

Antimalarials (Level of evidence = C)

Thalidomide (Level of evidence = C)

Griseofulvin (Level of evidence = D)

Mycophenolate mofetil (Level of evidence = E)

Low molecular weight heparin (Level of evidence = C)

Excimer laser (Level of evidence = C)

Oral retinoids and antimalarials have traditionally been the main systemic agents used in LPP, probably due to extrapolated data from trials in cutaneous LP. In an RCT of 65 patients with cutaneous LP, comparing acitretin with placebo, a 65% remission rate was seen in the treatment group.[162] Evidence in LPP is, however, poor, and the general concerns with retinoid therapy for patients with PCA listed above (see CCLE) apply. Of two patients with scalp involvement included in an open-label study (total n = 18) of low-dose tretinoin for LP, both showed a marked improvement with oral tretinoin (10–20mg daily for 1–10.5months).[163] Since then Reygagne reported eight patients with LPP treated with acitretin and found no response in any of the subjects.[164]

Antimalarials are common second-line agents in a number of centres to treat the lymphocyte-predominant subgroup of PCA.[165,166] Again, evidence that antimalarials work in LPP is poor. Mehregan et al.[151] treated nine patients and observed 'improvement' in 22%. There was reduction in symptoms but no change in disease progression. Tan et al.[165] reported using antimalarials in 19 of 25 (76%) patients with LPP. They comment that 9months is the minimum duration of treatment required before dose tapering is possible; unfortunately, no patient details or response rates were supplied. A clinical trial of hydroxychloroquine (400mg daily for 6months) in LPP found no response in any of the four patients treated.[167]

Thalidomide (100–150mg daily for 2–6months) has been reported as beneficial in two separate reports;[168,169] however, a very small open trial (n = 4) showed either no response or deterioration in the patients treated.[170]

Griseofulvin has been shown by RCT to be beneficial in cutaneous LP.[171] Two series (n = 4 and n = 10) in LPP suggest a 50% response rate with griseofulvin at >500mg daily in divided
doses.[151,172] Combination therapy with griseofulvin and oral steroids resulted in 'improvement' in one case.[173]

One patient showed complete remission with mycophenolate mofetil at a dose of 500mg twice daily for 6months without recurrence at 3months follow-up.[174]

An open study (n = 18) investigating low molecular weight heparin in various forms of LP reported a 'marked improvement' in one of three patients with scalp involvement treated with subcutaneous enoxaparin (3mg once weekly) for 6–13weeks,[175] with no response being seen in the other two patients.

Excimer laser (monochromatic 308-nm UVB) was studied in 13 patients with biopsy-proven, treatment-resistant LPP. Improvement was observed in three patients.[176]

Frontal fibrosing alopecia (FFA) was first described by Kossard in 1994.[177] It is characterized by progressive symmetrical recession of the frontal hairline revealing a pale band of skin (1–8cm), lacking follicular ostia. This pale skin contrasts with darker, sun-damaged skin on the forehead, with the zone of transition suggesting the location of the original hairline. Perifollicular inflammation and hyperkeratosis are often present but are confined to the immediate hairline. Eyebrow involvement, with decreased hair or complete loss, is very common and is regarded as a helpful diagnostic sign.[178] FFA tends to run a progressive course; however, stabilization seems to occur with time and patients with FFA that advances beyond the mid-frontal scalp are rare.[178] Most cases are seen in postmenopausal women. FFA is felt to be a variant of LPP and the histology findings are usually indistinguishable.[179]

Treatment. The protocol for classic LPP may be followed. The following options have been specifically described in FFA.

Intralesional triamcinolone acetonide (Level of evidence = D)

Finasteride (Level of evidence = D)

Oral corticosteroids (Level of evidence = D)

Antimalarials (Level of evidence = E)

Topical Corticosteroids (Level of Evidence = D)

Sixteen patients with FFA treated with ILTAC (20mgmL−1 every 3months) were followed for up to 48months. In all patients (except one who abandoned treatment) disease progression was halted. Finasteride (2.5mg daily) was given concomitantly when female pattern hair loss (FPHL) was present. FPHL improved with finasteride but it had no influence on the degree of FFA.[180] Others have reported benefit from ILTAC.[181]

Eight patients with FFA, without evidence of FPHL, were treated with finasteride (2.5mg daily). Arrest of disease progression, after 12–18months, was reported in four of eight patients.[182]

Oral corticosteroids slowed rapid hair loss in two of four patients[177,178] and halted hair loss in one patient.[183] However, further progression was seen when treatment was withdrawn.

Hydroxychloroquine (150mg daily) induced a 'temporary response' in one of three patients.[178] However, Vaisse et al.[184] reported no response in 13 patients treated with antimalarials.

All 23 patients, from two series, treated with topical corticosteroids showed no response to therapy.[178,184] Anecdotal reports have, however, suggested stabilization of disease with topical corticosteroids, sometimes used in combination with topical minoxidil lotion.[185,186]

GLS is a rare condition characterized by the triad of progressive scarring scalp alopecia, nonscarring loss of pubic and axillary hair and widespread keratosis pilaris (KP)-like horny follicular papules, that may resemble a severe case of seborrhoeic dermatitis. These three clinical manifestations, however, need not be present simultaneously.

Treatment. The protocol for classic LPP may be followed. The following options have been specifically described in GLS.

Topical PLUS intralesional corticosteroids (Level of evidence = E)[187,188]

Oral ciclosporin (Level of evidence = E)[189,190]

Systemic corticosteroids (Level of evidence = E) [191–193]

Topical tacrolimus (Level of evidence = E)[194]

Metronidazole (Level of evidence = E)[195]

Benefit has been reported for the above treatments – see cited references for details.

Brocq[196] first described pseudopelade (PB) in 1888. The term literally means 'pseudo alopecia areata' due to similarities with that condition. Opinions are still divided as to whether PB is a specific disease entity or just the end-stage appearance of other scarring disorders, particularly LPP and CCLE (Figure 3).[2] Diagnostic criteria have been published.[197]

Noninflamed patches of cicatricial alopecia indistinguishable from pseudopelade (histopathological diagnosis = lichen planopilaris).

PB is characterized by multifocal, asymptomatic, flesh-coloured patches of cicatricial alopecia. The appearances have been likened to 'footprints in the snow'.[198] The patches are often atrophic with no inflammation clinically apparent; however, early lesions may display slight scale and follicular erythema. The disease is slowly progressive with periods of activity and remission. Progressive hair loss and the ability to extract anagen hairs easily with gentle traction are often the only evidence that the disease is active. Spontaneous resolution has been reported after 2–18years of disease activity.[199]

Treatment. No clear treatment consensus is established for PB. One option is to follow the same protocol as classic LPP.[2] The following options have been specifically described in PB.

Potent topical corticosteroids (Level of evidence = D)

Hydroxychloroquine (Level of evidence = C)

Antibiotics if Borrelia positive (Level of evidence = E)

Thalidomide (?ineffective–Level of evidence = C)

In a large series of 94 patients with PB, all patients were treated with topical corticosteroids, with half having halting of disease progression within 22months. The authors did, however, concede that this observed 'response' might represent spontaneous remission.[199] Combination treatment of a potent topical steroid with an oral antihistamine (cetirizine) improved four patients with PB.[155]

Bulengo-Ransby and Headington[200] reported a child who improved with hydroxychloroquine. They claimed, in their experience, that hydroxychloroquine is the only effective treatment for PB; however, no further information was supplied.[201] Tan et al.[165] reported using hydroxychloroquine in 18 patients with PB but no details of response were supplied. New PB patches developed during hydroxychloroquine treatment in one report[202] and no response was seen in all four patients enrolled in a 6-month prospective study (400mg daily).[167]

In one patient with PB and borreliosis, disease progression was halted with a 3-week course of cefotaxime.[203] In a 6-month open trial, two patients were treated with thalidomide (100–200mg daily) without benefit.[170]

Central centrifugal cicatricial alopecia (CCCA) is a term that has been coined to encompass a number of previously described conditions including hot-comb alopecia[204] and follicular degeneration syndrome.[205,206] Most patients with CCCA are African-American women, although it can occur in men and in different ethnic groups.[207] CCCA is characterized by slowly progressive scarring of the crown and vertex that spreads in a symmetrical and centrifugal pattern, resulting in permanent alopecia. Although usually asymptomatic, unusual sensations, such as pins and needles, itch or tenderness may occur. The skin is smooth, shiny and noninflamed and often soft and supple to the touch. The alopecia is incomplete, with a number of hairs remaining within the area of scarring.

The pathogenesis of CCCA is unknown, but is likely to be multifactorial, with both genetic and environmental factors playing a role. This condition is often associated with traumatic hair-care practices, including hot-combing and the use of chemical relaxers; however, a definitive link has so far not been established.[208] The earliest histological feature is premature disintegration of the inner root sheath, resulting in outward migration of the hair shaft through the ORS at the level of the isthmus. Lamellar fibroplasias and lymphocytic inflammation surround the follicle at this level, resulting in follicular destruction and fibrous tract formation.[206]

Treatment.

Stop damaging hair-care practices (Level of evidence = E)

Potent topical steroid PLUS oral tetracycline antibiotic (Level of evidence = E)

Intralesional triamcinolone acetonide (Level of evidence = E)

Most authors recommend cessation of all traumatic hair-care practices,[204,206,208,209] although evidence of effectiveness of this intervention is lacking; CCCA may still progress despite this measure. Sperling et al.[207] recommend empirical treatment comprising the combination of a potent topical steroid with an oral tetracycline antibiotic, continued until the disease process is quiescent for 1year. No patient details were, however, supplied. Some authors recommend aggressive anti-inflammatory treatment comprising monthly ILTAC injections; but again, no patient details were supplied.[209]

Alopecia mucinosa (AM) is a rare clinicopathological entity that was first described by Pinkus in 1957.[210] AM is characterized by distinctive skin lesions associated with histological evidence of mucin deposition within the hair follicle. The term follicular mucinosis (FM) is commonly used interchangeably with AM; however, FM should be regarded as a histological reaction pattern seen in a number of conditions, and not as a specific disease entity per se.[211]

Clinically, AM presents with follicular papules that may coalesce into one or more erythematous, well-defined and indurated plaques. Close examination reveals prominent follicular openings with loss of hair. Alopecia is not always apparent, especially when nonhair-bearing sites are involved. Alopecia may be scarring or nonscarring. It may involve any part of the integument, with the face and neck being the commonest involved sites. Symptoms may include dysaesthesia and pruritus.[2]

Three clinical forms of AM are recognized. Group 1= lesions limited to the head and neck that resolve spontaneously within a few months. Group 2 = widespread lesions that run a chronic and relapsing course. Both group 1 and 2 occur in younger patients without a demonstrable underlying disease ('primary' AM). Group 3 = widespread lesions occurring in older patients that are often associated with an underlying lymphoproliferative disorder ('secondary' AM). Approximately 15% of patients will have mycosis fungoides.[212] Unfortunately clinical and histopathological features are not reliable predictors of disease course and prognosis, making differentiation of idiopathic from lymphoma-associated AM, on clinicopathological criteria, impossible.[213,214,215]

The key histological feature is mucinous degeneration of the ORS and sebaceous glands. A perifollicular lymphocytic infiltrate is usually found. Serial biopsies may be required if lymphomatous change is suspected, especially if there is clinical disease progression.

The aetiology of AM is unknown. It has been proposed that an unknown antigen stimulates a T-cell response directed against the hair follicle, with resulting mucin deposition and follicular
destruction.[216,217]

Treatment. The possibility of spontaneous remission makes observation, without treatment, an option in some patients;[212] however, long-term follow-up is recommended so as not to miss those progressing to lymphoma.[213,215] In secondary AM the underlying condition must be treated. The following treatment options are for primary AM only.

First-line treatment.

Potent topical corticosteroids (Level of evidence = D)

Eight of 10 patients reportedly responded to topical corticosteroids; however, the treatment regimen was not described.[212] Three of three patients with localized disease, and nine of 15 with generalized disease cleared with topical corticosteroids.[218] Others have also reported
benefit.[216,219,220]

Second-line treatment.

Intralesional triamcinolone acetonide (Level of evidence = D)

Tetracycline antibiotics (Level of evidence = E)

Topical±oral indometacin (Level of evidence = E)

Dapsone (Level of evidence = E)

ILTAC resulted in clearance in a small number of patients with both localized and generalized disease.[218] One other patient cleared with a 6-month course of biweekly ILTAC injections.[221] Minocycline is proposed to be beneficial in a number of reports.[222,223,224,225] Indometacin 1% gel applied twice daily, combined with oral indometacin in one case, improved two patients.[226,227] Dapsone (100mg daily) may be beneficial; however, continued treatment may be necessary to maintain remission.[219,228,229]

Third-line treatment.

Systemic steroids (Level of evidence = E) [221,230,231,232]

Isotretinoin (Level of evidence = E)[233,234]

PUVA/ultraviolet A1 (Level of evidence = E)[235,236]

Superficial X-ray therapy (Level of evidence = D)[210,212,218,221,224]

Excision (Level of evidence = E)[217]

Antimalarials (Level of evidence = E)[237]

Interferon alfa-2b PLUS interferon-γ (Level of evidence = E)[238]

Benefit has been reported for the above treatments – see cited references for details.

Keratosis follicularis spinulosa decalvans (KFSD) is a rare condition characterized by widespread KP and scarring alopecia. KFSD has three main stages of development: onset occurs in infancy with KP developing on the face; a second active stage then ensues during childhood and early adolescence where progressive scarring alopecia develops; the final stage, characterized by clinical improvement, generally occurs after puberty. Variable degrees of hyperkeratosis, inflammation and atrophy are seen and the scarring may be patchy or diffuse.[239] Secondary infections, manifesting as scalp pustules, are common, difficult to control and may exacerbate the scarring process. Less common features include photophobia, ocular abnormalities (particularly corneal dystrophy), focal palmoplantar keratoderma and atopy. The commonest mode of inheritance is X-linked dominant; however, sporadic cases may occur.[240]

KFSD is part of the heterogeneous group of disorders termed keratosis pilaris atrophicans.[241] The three main entities are KFSD, keratosis pilaris atrophicans faciei (=ulerythema ophyryogenes) and atrophoderma vermiculatum. These conditions are distinguished by their location and the degree of inflammation and atrophy. Only KSFD causes scarring alopecia. Histological features include follicular hyperkeratosis and scarring but with preservation of sebaceous glands. Aetiology is unknown but it may represent a disorder of keratinization.

Treatment. Evidence for treatment is poor. The following options have been described in KFSD.

Potent topical corticosteroids±keratolytics (Level of evidence = E)

Oral antibiotics for pustular flares (Level of evidence = D)

Dapsone (Level of evidence = E)

Laser epilation (Level of evidence = E)

Oral retinoids (Level of evidence = E)

Partial improvement was seen in nine patients treated with topical corticosteroids, with recurrence observed with treatment withdrawal.[241] Topical tretinoin 0.1% combined with a 'topical corticosteroid' for 3months, was used in two other patients, with some improvement.[241]

Oral antibiotics, preferably based on culture and sensitivities, appear to improve pustular
flares;[241,242,243] however, pustules may only resolve once all the hair has been lost. Dapsone (100mg daily) halted progression and reduced inflammation in one patient.[244] Laser epilation at 6-weekly intervals reduced inflammation but resulted in permanent hair loss.[245]

Two patients reportedly achieved remission after 12weeks of treatment with etretinate 0.8mgkg−1 or isotretinoin 0.5mgkg−1.[246] Good control of inflammation and pustules was achieved in a 12-year-old using isotretinoin 0.6mgkg−1 daily for 20weeks.[247] Most reports, however, do not show benefit from this treatment.[241,243,244,248–250] Herd and Benton[250] suggest that treatment is only likely to be effective when given during the active phase of the disease, which they feel may explain some of the reported treatment failures with retinoids.

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