Erosive pustular dermatosis of the scalp

INTRODUCTION — Erosive pustular dermatosis of the scalp (EPDS) is a rare, inflammatory scalp condition characterized by skin atrophy, erosions, and thick crusts that results in permanent hair loss (picture 1A-E). EPDS classically occurs in older adults but can also occur in younger individuals [1]. The etiology is poorly understood, but there is often a history of trauma or actinic damage in the affected area. Although some patients respond well to topical corticosteroids or topical tacrolimus, a chronic waxing and waning course is not unusual.

The evaluation and management of EPDS will be described here (algorithm 1). Other inflammatory and scarring disorders of the scalp are reviewed separately. (See "Evaluation and diagnosis of hair loss", section on 'Cicatricial alopecia'.)

EPIDEMIOLOGY — EPDS is rare; the prevalence and incidence are not known. Most epidemiologic data come from case series of 10 to 50 patients. EPDS appears to be most common in older adults but has also occurred in younger adults and children [1-4]. A systematic review of the literature that identified reports of 168 patients with EPDS found a median patient age of 76 years (interquartile range 62 to 81 years) [5]. Among the patients with documentation of sex, 97 patients were male, and 70 patients were female.

PATHOGENESIS — The pathogenesis of EPDS is unclear. While there may be many contributory factors, most reports cite four main elements: scalp trauma or local damage to the skin, skin atrophy, an altered and prolonged immune response, and resultant healing with cutaneous scarring and permanent hair loss [3,4,6].

Preceding damage to the scalp can be identified in almost all patients [3-8]. Examples of types of local scalp damage, trauma, and disorders that have been reported to precede EPDS include:

●Actinic damage – Multiple reports cite actinic damage as the predisposing factor for local skin atrophy and EPDS [4,6,7,9].

●Androgenetic alopecia – Longstanding androgenetic alopecia may contribute through increasing actinic damage in the area of hair loss [3,10,11].

●Procedures or trauma – EPDS has occurred following medical procedures and other scalp trauma. Examples include surgery, hair transplants, laser treatment, radiation therapy, photodynamic therapy, cryotherapy, and a chemical burn [12-19].

●Drugs – The disease has also been associated with use of topical drugs that may induce skin inflammation, such as fluorouracil, imiquimod, tretinoin, minoxidil, latanoprost, and ingenol mebutate [11,12,20-23]. Moreover, there are case reports describing systemic treatment with epidermal growth factor receptor inhibitors as a contributing factor [24-26].

●Disease states – Examples of disease states that have preceded EPDS include herpes zoster, contact dermatitis, and aplasia cutis congenita [27-31].

The time between the initial trauma and onset of EPDS is highly variable, ranging from weeks to years [2,32]. It is postulated that damage to the scalp leads to skin atrophy [4]. Atrophic skin displays delayed wound healing, which may lead to persistent erosions in EPDS. The persistence of open, crusted areas likely stimulates an altered immune response to skin and hair follicles in the affected area. Healing occurs with scarring, which destroys hair follicles and leads to permanent alopecia and further skin atrophy.

The role of inflammation as a key component of the pathogenesis of EPDS is supported by clinical findings of abundant crusting, evidence of notable inflammation in biopsy specimens, and the responsiveness of EPDS to potent topical corticosteroids [7]. Some authors hypothesize that EPDS is an autoimmune phenomenon, but specific antigens have not been identified.

CLINICAL MANIFESTATIONS — The vertex and crown of the scalp are common sites for EPDS; less frequently, other areas of the scalp are involved [3]. Often the involved area is linear, oriented from the front to the back of the scalp (picture 1D-E). Alternatively, it may appear round, triangular, or mirror the distribution of the previous trauma [3].

The clinical findings vary depending on the stage of evolution. Early on, there is cutaneous erythema with serous or hemorrhagic crusting. Patients subsequently develop thick, yellow-brown crusts and erosions (picture 1E). Later, there is prominent scarring hair loss, skin atrophy, and varying amounts of yellow-brown crusts located centrally or at the margin of the patch of alopecia (picture 1A-C, 1E). Intact pustules are rare despite the name "erosive pustular dermatosis of the scalp."

EPDS is typically asymptomatic, but some patients may experience pain, burning, or pruritus.

PATHOLOGY — Similar to the clinical features, pathologic features of EPDS vary based upon the stage of development [3]. There are no pathognomonic, pathologic findings. Biopsy specimens show varying degrees of atrophy; a mixed, inflammatory infiltrate; and scarring hair loss. These features may be seen in other inflammatory conditions and other forms of alopecia and are not entirely diagnostic [4,6,9].

Histopathologic findings can vary depending on the stage of EPDS when biopsied:

●Early stage (cutaneous erythema with prominent crusting) – Histopathologic findings include psoriasiform hyperplasia of the epidermis and hyperkeratosis of the stratum corneum. There is often a mixed, inflammatory infiltrate in the dermis, comprised of lymphocytes, neutrophils, and plasma cells. There may be mild, perifollicular fibroplasia with increased catagen/telogen counts but normal density of follicles [3,12].

●Middle stage (thick, yellow-brown crusts with evolving scarring and hair loss) – There is psoriasiform epidermal hyperplasia and hyperkeratosis as well as abundant scale crust and parakeratosis. Extensive fibrosis of the dermis begins, demonstrating decreased density of follicles and loss of sebaceous glands. There can be fusion of hair follicles (polytrichia or tufting) and destruction of the hair follicle epithelium [3,12].

●Late stage (prominent scarring and skin atrophy) – The epidermis is atrophic. The dermis displays diffuse fibrosis with near complete absence of hair follicles and sebaceous glands [3,12].

DIAGNOSIS — There is no single diagnostic finding or test that confirms EPDS. The diagnosis is made through recognition of supportive history, physical, dermoscopic, and biopsy findings and the exclusion of other conditions. Cultures may be needed to rule out infection.

History — The patient history should include assessment for a history of trauma to the scalp to identify potential contributory factors for EPDS. Patients should be asked about:

●Scalp injury or preceding procedures on the scalp

●Pharmacologic therapies applied to the scalp

●Pre-existing skin disorders on the scalp (eg, actinic keratoses or androgenetic alopecia) (see 'Pathogenesis' above)

Physical examination — The physical examination should incorporate a careful evaluation of the scalp as well as the rest of the skin and mucous membranes. In particular, findings of significant crusts, erosions, and scarring hair loss in the setting of skin atrophy or significant actinic damage support the diagnosis. Involvement of the mucous membranes or the skin elsewhere on the body suggests an alternative diagnosis. (See 'Clinical manifestations' above and 'Differential diagnosis' below.)

Dermoscopy — Dermoscopy of the hair and scalp (also known as trichoscopy) can be helpful in the diagnosis of EPDS [3,24,33]. In the inflammatory areas, dermoscopic findings include serous or pigmented crusts. In the areas of hair loss, typical findings include loss of follicular ostia and tufting of up to several hairs. Due to skin atrophy, dermal vessels appear enlarged. Visualization of the hair bulbs through skin was previously only described in aplasia cutis congenita and may be one of the more specific findings of EPDS [33]. (See "Overview of dermoscopy" and "Overview of dermoscopy of the hair and scalp".)

Biopsy — A biopsy is useful for the identification of histologic features consistent or inconsistent with EPDS but is not diagnostic without correlation with the history and clinical findings. The biopsy should be taken from an area of active inflammation where there are still intact hair follicles. A biopsy from the middle of a longstanding area of scarring or alopecia will show scar and loss of follicles. (See 'Pathology' above.)

A 4 mm punch biopsy is usually sufficient. A second 4 mm punch biopsy for direct immunofluorescence is suggested particularly if there are erosions present or the pathology results are suggestive of an autoimmune blistering disease. (See "Skin biopsy techniques", section on 'Punch biopsy' and 'Differential diagnosis' below.)

Culture — The crusting associated with EPDS can be difficult to distinguish from primary or secondary infection. In the absence of infection, cultures of EPDS are sterile or demonstrate normal skin flora. A swab specimen for bacterial culture aids in identifying patients who require treatment of infection. We perform cultures when patients exhibit pain, pustules, or other features less typical for EPDS. (See 'Differential diagnosis' below.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of EPDS is broad. Multiple inflammatory, infectious, neoplastic, and factitial conditions may present with erosions, pustules, crusting, or alopecia of the scalp [2].

Relatively common disorders to consider in the differential diagnosis of EPDS include:

●Squamous cell carcinoma – Squamous cell carcinoma is a common form of skin cancer and is most often diagnosed in sun-exposed areas. Squamous cell carcinoma of the scalp may mimic EPDS, presenting with a crusted, hyperkeratotic, or eroded plaque (picture 2). A skin biopsy shows an invasive, atypical, epithelial proliferation and distinguishes squamous cell carcinoma from EPDS. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis".)

●Basal cell carcinoma – Basal cell carcinoma is common in actinically damaged skin of older patients, including on the scalp. Basal cell carcinoma characteristically presents as a shiny or pearly, pink or red papule or plaque but rarely appears as a crusted or ulcerated plaque that may be mistaken for EPDS. A skin biopsy showing a malignant neoplasm comprised of basaloid islands with peripheral palisading confirms the diagnosis. (See "Basal cell carcinoma: Epidemiology, pathogenesis, clinical features, and diagnosis".)

●Bacterial infection – Bacterial folliculitis and impetigo can present as perifollicular pustules or crusts on the scalp. Distinct from EPDS, associated alopecia is unusual, and bacterial culture is positive, usually showing the causative organism Staphylococcus aureus. (See "Infectious folliculitis", section on 'Bacterial folliculitis'.)

●Tinea capitis – Tinea capitis is a fungal infection on the scalp that can develop into an abscess (kerion) as a result of a marked, inflammatory response. Clinical examination findings of kerion include a boggy, inflamed plaque with purulent drainage and hair loss (picture 3). Regional lymph nodes of the neck are frequently enlarged. Unlike EPDS, tinea capitis most often occurs in children. A fungal culture can confirm the diagnosis [34]. (See "Tinea capitis".)

Less common disorders in the differential diagnosis include autoimmune blistering diseases, discoid lupus erythematosus, folliculitis decalvans, pyoderma gangrenosum, dermatitis artefacta, and halogenoderma:

●Autoimmune blistering diseases:

•Localized cicatricial pemphigoid (Brunsting-Perry type) – Localized cicatricial pemphigoid may present on the scalp of older adults. Intact blisters are uncommon, and patients usually present with erosions, scarring, or alopecia of the scalp (picture 4). The clinical presentation can be similar to EPDS, so a biopsy and immunofluorescence testing is essential. The biopsy demonstrates a subepidermal blister, often with eosinophils. Direct immunofluorescence is essential for the diagnosis and demonstrates linear deposition of immunoglobulin G (IgG) or complement along the basement membrane zone [35]. (See "Clinical features and diagnosis of bullous pemphigoid and mucous membrane pemphigoid".)

•Pemphigus foliaceus – Flaccid blisters or crusted erosions on the head, neck, and upper trunk are common in pemphigus foliaceus. Unlike EPDS, lesions outside of the scalp are common. The diagnosis is made based upon biopsies for histology and direct immunofluorescence that demonstrate subcorneal blistering with acantholysis and intercellular deposition of IgG and complement in the epidermis, respectively [36]. (See "Pathogenesis, clinical manifestations, and diagnosis of pemphigus", section on 'Pemphigus foliaceus'.)

•Pemphigus vulgaris – Pemphigus vulgaris may present with lesions on the scalp. Flaccid blisters, crusts, or erosions are also typically seen in the mouth or elsewhere on the body, helping to distinguish it from EPDS. The diagnosis is made based upon biopsies for histology and direct immunofluorescence that demonstrate suprabasilar bullae with acantholysis and intercellular deposition of IgG and complement in the epidermis, respectively [37]. (See "Pathogenesis, clinical manifestations, and diagnosis of pemphigus", section on 'Pemphigus vulgaris'.)

●Discoid lupus erythematosus – Discoid lupus erythematosus is a chronic, cutaneous form of lupus erythematosus that frequently involves the scalp and is a common cause of cicatricial alopecia. Clinical examination demonstrates erythematous, atrophic or scaly patches or plaques; hyperpigmentation at the margins of the plaques; and follicular plugging (picture 5). Unlike EPDS, discoid lupus erythematosus often also involves the nose, face, or concha of the ears. A biopsy is helpful for the diagnosis, and findings include a superficial and deep, lymphocytic infiltrate; mucin deposition; and interface alteration [38]. (See "Overview of cutaneous lupus erythematosus", section on 'Discoid lupus erythematosus'.)

●Folliculitis decalvans – Folliculitis decalvans is a neutrophilic, primary, cicatricial alopecia. Clinical findings supportive of folliculitis decalvans include a patch of scarring alopecia with perifollicular pustules and crusts on the scalp (picture 6). Tufting of hairs (multiple hairs emanating from one follicle) is characteristic [39]. Unlike EPDS, there is not usually a history of preceding trauma or damage to the scalp, and prominent skin atrophy is not common. (See "Folliculitis decalvans".)

●Pyoderma gangrenosum – Pyoderma gangrenosum is a neutrophilic dermatosis that may start as a pustule but then rapidly enlarges to painful ulcers with rolled or undermined borders. A biopsy shows an ulcer with a predominantly neutrophilic infiltrate [40]. (See "Pyoderma gangrenosum: Pathogenesis, clinical features, and diagnosis".)

●Dermatitis artefacta – In dermatitis artefacta, skin changes are caused solely by the patient manipulating their own skin. Clinical findings include erythematous patches, plaques, erosions, or ulcers, which are characteristically angulated or bizarre shaped. In contrast to EPDS, dermatitis artefacta is most common in young females or patients with psychologic disorders [41].

●Halogenoderma – Halogenoderma is a rare, inflammatory skin condition caused by accumulation of natural elements or halogens, such as iodine or bromide, in the body [42]. Characteristic examination findings vary and include acne-like papules, crusted plaques, erosions or ulcers, and blisters. The diagnosis is made by eliciting a history of halogen exposure and/or high levels of halogens in the blood. (See "Drug eruptions", section on 'Halogens'.)

TREATMENT — EPDS can be a chronic, recalcitrant condition that negatively impacts quality of life. Therefore, treatment is generally indicated.

Principles — The goals of treatment are to reduce inflammation, promote healing of erosions, and halt the progression of scarring hair loss. Early treatment is desirable to minimize permanent hair loss.

The three major components of the therapeutic approach include patient counseling, protective measures, and medical therapy (algorithm 1). Due to the rarity of EPDS, data on treatment are limited. No randomized trials have been performed, and treatment recommendations are based upon observations from case reports and case series [5]. A systematic review that included reports published up to June 2019 found insufficient data for a meta-analysis [5].

Patient counseling — Patients with EPDS should be carefully counseled to ensure realistic expectations for treatment. While some patients respond well within several months of treatment, the disease can recur and can be refractory. In addition, patients with scarring hair loss should be informed that hair regrowth is not expected in scarred areas.

Protective measures — Protective measures aimed at promoting healing are considered an important component of treatment. Examples include avoidance of sun exposure and limiting of physical trauma to the scalp by avoiding insults such as hot hair dryers, harsh combing, and chemical treatments such as dyes and perms [3]. Bland wound dressings and silicone gels may also be helpful for healing [43].

Initial medical therapy — Topical corticosteroids and topical tacrolimus (a topical calcineurin inhibitor) are accepted options for first-line therapy (algorithm 1). (See 'Topical corticosteroids' below and 'Topical tacrolimus' below.)

General approach — Topical corticosteroids are frequently less expensive than topical calcineurin inhibitors and are often tried first for this reason (algorithm 1). However, if significant, EPDS-related skin atrophy is present, we avoid topical corticosteroids and proceed directly to topical tacrolimus therapy. Topical corticosteroids may worsen cutaneous atrophy. (See "Topical corticosteroids: Use and adverse effects", section on 'Cutaneous'.)

Our suggested approach to patients without significant, EPDS-related skin atrophy is as follows:

●Daily application of the high-potency corticosteroid for four weeks. If improvement (reduction in erythema, erosions, crusting) occurs, application of the topical corticosteroid should be gradually reduced to the lowest frequency that maintains progressive improvement. Once resolution of crusts, erosions, and significant erythema has occurred, the topical corticosteroid can be discontinued.

●If improvement is occurring but longer than eight weeks of daily or every-other-day topical corticosteroid therapy is needed, we incorporate topical tacrolimus 0.1% ointment as a corticosteroid-sparing therapy (eg, application of topical tacrolimus five days per week and application of the topical corticosteroid two days per week) or transition to topical tacrolimus monotherapy. (See 'Topical tacrolimus' below.)

●If signs of improvement are not present after eight weeks of high-potency corticosteroid therapy, treatment is unlikely to be effective. The topical corticosteroid can be discontinued and topical tacrolimus 0.1% ointment initiated. (See 'Topical tacrolimus' below.)

Topical corticosteroids

●Administration – Topical corticosteroid therapy involves application of a high-potency (group 1 or 2 (table 1)) topical corticosteroid (eg, clobetasol propionate 0.05% ointment) to the affected area on the scalp once or twice per day [3,6,12,44,45].

Although weeks to months of treatment may be necessary to achieve healing, the risk for corticosteroid-induced cutaneous atrophy limits the duration of treatment. Efforts should be made to taper frequency of topical corticosteroid use once improvement occurs. At least partial improvement is expected within eight weeks. (See 'General approach' above.)

●Efficacy – Observations from a case series of 20 patients with EPDS who applied either clobetasol propionate 0.05% ointment (17 patients) or tacrolimus 0.1% ointment (3 patients) support benefit of topical corticosteroid therapy [3]. Medication was applied at night and washed off in the morning, and the frequency of application was gradually reduced upon recognition of improvement. Disappearance of crusts and erosions and a reduction in scalp erythema occurred in 14 of 17 patients treated with clobetasol propionate and all 3 patients treated with topical tacrolimus. The mean duration of time until efficacy was five months. Seven patients relapsed between two and eight months after treatment; however, relapses were milder than initial disease and responded to topical corticosteroid therapy.

Topical corticosteroids are the most frequently reported therapies for EPDS. In a review of published case reports and case series through June 2019, documentation of complete resolution was present in 32 of 79 cases in which outcomes of topical corticosteroid monotherapy were reported [5]. The average duration of topical corticosteroid therapy was six weeks.

●Adverse effects – Topical corticosteroids, particularly high-potency topical corticosteroids, may induce cutaneous atrophy and other cutaneous adverse effects. Hypothalamic-pituitary axis suppression may occur with chronic use on large or highly permeable areas. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

Topical tacrolimus

●Administration – Topical tacrolimus 0.1% ointment is applied to the affected scalp once or twice daily.

To achieve healing, treatment typically needs to be continued for weeks to months [3,27,46-49]. At least partial improvement is expected within eight weeks. (See 'General approach' above.)

●Efficacy – Case reports and case series describing benefit of topical calcineurin inhibitor therapy have generally involved use of topical tacrolimus 0.1% ointment [3,27,46-49]. A systematic review of the literature through June 2019 identified 10 patient reports of complete resolution with topical tacrolimus monotherapy in addition to three reports of partial resolution and one report of recurrence [5]. The median duration of treatment was eight weeks.

●Adverse effects – Common side effects of topical calcineurin inhibitors include burning or stinging at the site of application. Although concern for increased risk for cancer led the US Food and Drug Administration (FDA) to place a boxed warning on the prescribing information for topical calcineurin inhibitors, a causal relationship has not been established. (See "Treatment of atopic dermatitis (eczema)".)

Relapses — Relapses can be treated with a repeat course of topical corticosteroid or topical calcineurin inhibitor therapy, if previously effective. Patients with recurrent relapses may benefit from a maintenance regimen aimed at reducing risk for relapse, typically application of tacrolimus 0.1% ointment two to seven days per week [3,46].

Refractory disease — Patients who cannot achieve satisfactory improvement with topical corticosteroids or calcineurin inhibitors may benefit from other therapies (algorithm 1). Data on these treatment options are primarily limited to case reports and small case series [5]. Selection is based upon factors such as comorbidities, patient risk tolerance, and treatment feasibility:

●Systemic glucocorticoids – Patients with refractory EPDS are often given a short course of systemic glucocorticoid therapy. Adults may respond to 15 to 40 mg of prednisone per day given for up to several weeks [3,7,45,48]. A reasonable regimen consists of an initial dose of 0.5 to 1 mg/kg of prednisone, tapered to discontinuation over four to eight weeks. Long-term therapy with systemic glucocorticoids is typically avoided because of risk for adverse effects. (See "Major adverse effects of systemic glucocorticoids".)

●Photodynamic therapy – Photodynamic therapy involves the administration of a topical photosensitizing drug prior to illumination with visible light. Benefit of photodynamic therapy for EPDS is documented in case reports and a case series [5]. In a series in which eight patients with EPDS were treated with gentle curettage of hyperkeratotic lesions followed by photodynamic therapy one to two weeks later, six patients had resolution of lesions within six weeks after treatment, and the remaining two patients achieved resolution after a second treatment [50]. However, photodynamic therapy has also been reported as an inciting cause of EPDS [51,52]. (See "Photodynamic therapy".)

●Other therapies – Other therapies reported effective for individual patients include intralesional administration of corticosteroids and once- or twice-daily application of topical calcipotriol, topical antibiotics, topical dapsone, or a topical retinoid [45,53,54]. Oral therapies that may have led to improvement in patients with EPDS include doxycycline (100 mg twice daily), isotretinoin (0.75 mg/kg per day), acitretin (50 mg per day), dapsone (up to 100 mg per day), zinc (180 to 600 mg per day), methotrexate, oral calcineurin inhibitors, and tofacitinib [5,7,45,55-59].

Laser, surgical excision, and superficial radiation therapy have been used as a treatment of last resort for patients who fail to respond to other therapies [5,50,60]. Caution is prudent, as these interventions have also been reported as causes of EPDS. (See 'Pathogenesis' above.)

PROGNOSIS AND FOLLOW-UP — Data are insufficient for conclusions about prognostic factors for EPDS. Clinical experience suggests that while some patients respond well to topical corticosteroids or topical tacrolimus and achieve durable remission within weeks to months, others experience a more chronic, recalcitrant course [3,5].

Periodic follow-up is recommended to assess the response to treatment and detect early signs of relapse. Given that EPDS often occurs in actinically damaged skin and shares clinical features with nonmelanoma skin cancer, patients should also receive regular surveillance for skin cancer.

SUMMARY AND RECOMMENDATIONS

●Overview – Erosive pustular dermatosis of the scalp (EPDS) is a rare scalp disorder characterized by the development of erosions, crusts, and scarring alopecia. EPDS most often occurs in older adults. (See 'Epidemiology' above.)

●Pathogenesis – The pathogenesis of EPDS is not well understood. Trauma to the skin, atrophy, inflammation, and altered wound healing are considered contributory factors. A history of damage to the scalp can be identified in almost all patients. EPDS has been reported to occur in association with actinic damage, androgenetic alopecia, scalp injuries or trauma, topical drugs, and disease states. (See 'Pathogenesis' above.)

●Clinical manifestations – EPDS most often involves the vertex or crown of the scalp. Classic findings include erythema, yellow-brown crusts, erosions, and hair loss in a linear or other distribution. Persistent disease results in permanent alopecia. (See 'Clinical manifestations' above.)

●Diagnosis – EPDS is diagnosed based upon recognition of supportive history, physical and pathologic findings, and the exclusion of other disorders. There are no pathognomonic findings. (See 'Diagnosis' above.)

●Management – Data on the treatment of EPDS are limited. A wide variety of topical and systemic agents have been utilized (algorithm 1).

We suggest use of a high-potency topical corticosteroid or tacrolimus 0.1% ointment for first-line treatment (Grade 2C). Patients who fail to respond to both of these interventions may benefit from treatments for refractory disease, such as systemic glucocorticoids, photodynamic therapy, and other therapies. Protection of the scalp from additional trauma and sun damage is an additional, important component of treatment. (See 'Treatment' above.)