INTRODUCTION — Pityriasis lichenoides is a term used to refer to a group of rare acquired inflammatory skin disorders that includes pityriasis lichenoides chronica (PLC), pityriasis lichenoides et varioliformis acuta (PLEVA), and the febrile ulceronecrotic Mucha-Habermann disease (FUMHD) variant of PLEVA. The use of the term pityriasis lichenoides to refer to all three disorders is representative of the theory that PLC, PLEVA, and FUMHD may represent a clinical spectrum of a single disease.

PLC is clinically characterized by the development of multiple scaly, erythematous to brown papules on the trunk and extremities. The condition usually has a relapsing and remitting course that persists for months or years.

The clinical manifestations, diagnosis, and management of PLC will be reviewed here. PLEVA is discussed separately. (See "Pityriasis lichenoides et varioliformis acuta (PLEVA)".)

EPIDEMIOLOGY — Definitive conclusions on the epidemiology of pityriasis lichenoides chronica (PLC) are hindered by the frequent lack of distinction between the subtypes of pityriasis lichenoides in the published literature and limited data. In general, PLC is considered a rare disorder that is most likely to occur in young adults and children [1]. However, PLC may develop at any age.

The existence of sex, ethnic, or racial predilections in PLC is uncertain [2]. Based upon data from a few retrospective studies of children with pityriasis lichenoides, there may be a slight male predilection for pityriasis lichenoides in the pediatric population [3-7]. In one of the largest series of children with PLC (n = 46), 59 percent of the children were male [4].

PATHOGENESIS — The pathogenesis of pityriasis lichenoides chronica (PLC) is poorly understood. Concordant with the view that PLC and pityriasis lichenoides et varioliformis acuta (PLEVA) may be related disorders, the major pathogenic theories for PLC and PLEVA overlap. These theories include the classification of PLC and PLEVA as hypersensitivity responses to infection or as primary lymphoproliferative disorders. (See "Pityriasis lichenoides et varioliformis acuta (PLEVA)", section on 'Pathogenesis'.)

Consideration of an infectious trigger for pityriasis lichenoides arises from reports of the occurrence of PLC or PLEVA in the setting of infection (eg, Toxoplasma gondii, Epstein-Barr virus, parvovirus B16, HIV, staphylococci, Group A streptococci, others) [2,8-11]. In addition, the relatively young age of onset and an observation of a familial outbreak of PLEVA have led some authors to propose infection as a trigger for pityriasis lichenoides [2,12].

The theory that PLC is a primary lymphoproliferative disease is based upon studies demonstrating clonal CD4⁺ T cell populations in tissue samples from patients with PLC and PLEVA [13,14]. However, monoclonality is not uniformly detected in PLC; in one study, only 1 of 13 PLC specimens demonstrated a monoclonal T cell receptor gene rearrangement [15]. Moreover, the detection of monoclonality is not sufficient to designate a disorder as a primary lymphoproliferative disease [15].

Occasionally, PLC has been reported to occur in association with drug exposure [16-18]. The mechanisms through which drugs might induce PLC are unknown.

CLINICAL FEATURES — The development of pityriasis lichenoides chronica (PLC) usually is gradual. Patients develop numerous red-brown papules that often demonstrate a characteristic overlying mica-like scale (picture 1A-C). Lesions in different stages of development are present simultaneously.

The trunk, buttocks, and proximal extremities are the most common sites of involvement. However, other cutaneous areas may be affected. Although the eruption usually is asymptomatic, associated pruritus occurs in some patients.

Patients with PLC typically exhibit a relapsing and remitting disease course that lasts for months to years. In a retrospective study of 46 children with PLC, the median duration of disease was 20 months (range 3 to 132 months) [4]. Individual lesions heal over several weeks leaving hypopigmented or hyperpigmented macules or patches [2]. Scarring is absent. Occasionally, patients present with widespread hypopigmented macules as the predominant clinical manifestation of the disease (picture 2) [19,20].

HISTOPATHOLOGY — Compared with pityriasis lichenoides et varioliformis acuta (PLEVA), the pathologic findings of pityriasis lichenoides chronica (PLC) are less pronounced. (See "Pityriasis lichenoides et varioliformis acuta (PLEVA)", section on 'Histopathology'.)

The characteristic pathologic features of PLC include [21]:

●Parakeratosis

●Mild spongiosis

●Minimal lymphocyte exocytosis

●Minimal vacuolar change and focal necrotic keratinocytes at the dermoepidermal junction

●Perivascular and lichenoid (band-like) lymphohistiocytic infiltrate in the superficial dermis

●A few extravasated erythrocytes in the papillary dermis

DIAGNOSIS — A diagnosis of pityriasis lichenoides chronica (PLC) is usually suspected based upon the clinical appearance. We typically perform a skin biopsy to confirm the diagnosis.

A 4 mm punch biopsy of a papule usually provides a specimen that is sufficient for the histologic evaluation for PLC. (See 'Histopathology' above and "Skin biopsy techniques", section on 'Punch biopsy'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of pityriasis lichenoides chronica (PLC) includes other disorders that may present with widespread papules or small plaques. A skin biopsy often is useful for distinguishing PLC from other diseases.

Examples of disorders that may resemble PLC include:

●PLEVA – Although pityriasis lichenoides et varioliformis acuta (PLEVA) and PLC are often considered to be related disorders, the clinical and pathologic features of PLEVA allow for the distinction between PLEVA and PLC. In contrast to the indolent course and red-brown, scaly papules of PLC, PLEVA is characterized by the acute onset of hemorrhagic and crusted papules (picture 3). In addition, pathologic findings of a dense, wedge-shaped lymphohistiocytic infiltrate in the dermis, necrosis, vesiculation, and dermal hemorrhage support a diagnosis of PLEVA rather than PLC. (See "Pityriasis lichenoides et varioliformis acuta (PLEVA)".)

●Pityriasis rosea – Pityriasis rosea is a papulosquamous eruption that usually presents with the acute development of numerous ovoid, erythematous patches with trailing scale on the trunk and proximal extremities (picture 4). A larger patch or plaque ("herald patch") may precede the more extensive eruption. Similar to PLC, children and young adults are most commonly affected. The course of pityriasis rosea tends to be shorter than PLC, with most cases resolving within four to six weeks. Occasionally, the eruption persists for longer. (See "Pityriasis rosea".)

●Guttate psoriasis – Guttate psoriasis is a form of psoriasis characterized by the acute development of multiple papules and small plaques with scale on the trunk and extremities (picture 5). Most cases occur in children or young adults, and the eruption is often preceded by a streptococcal infection. Untreated, guttate psoriasis usually persists for several weeks to several months. (See "Guttate psoriasis".)

●Lichen planus – Lichen planus is a chronic disorder characterized by the development of violaceous, polygonal papules with fine white scales (picture 6A-B). A lace-like pattern (Wickham's striae) may be evident on the surface of lesions. Unlike PLC, pruritus typically is prominent. Patients with lichen planus may develop additional lesions in sties of trauma (Koebner phenomenon). Oral, genital, or nail abnormalities may also be present. (See "Lichen planus".)

●Secondary syphilis – Cutaneous involvement in secondary syphilis may present with the development of slightly scaly, erythematous to brown macules, papules, or small plaques in a generalized distribution (picture 7). Involvement of the palms and soles is a common feature that suggests this diagnosis. Serologic studies are useful for confirming a diagnosis of syphilis. (See "Syphilis: Epidemiology, pathophysiology, and clinical manifestations in patients without HIV", section on 'Clinical manifestations'.)

●Lymphomatoid papulosis – Lymphomatoid papulosis is a rare variant of the primary cutaneous T cell lymphomas that present with crops of red papules on the trunk and extremities that resolve spontaneously over four to six weeks (picture 8). Most papules ulcerate and heal with scarring, unlike PLC, which usually heals with dyspigmentation only. (See "Lymphomatoid papulosis".)

●Hypopigmented mycosis fungoides – Postinflammatory hypopigmentation secondary to PLC can closely resemble hypopigmented mycosis fungoides, an uncommon presentation of mycosis fungoides characterized by generalized hypopigmented patches (picture 9). This concept was demonstrated in a Singaporean retrospective study that found that 24 percent of 46 children with mycosis fungoides were given an initial clinical diagnosis of PLC prior to performance of a biopsy [22]. Hypopigmented mycosis fungoides most commonly occurs in juvenile mycosis fungoides or as a presentation of mycosis fungoides in individuals with dark skin [23]. A skin biopsy demonstrating findings consistent with mycosis fungoides (eg, atypical lymphocytes, epidermotropism, and individual lymphocytes within the epidermis surrounded by vacuolated halos) helps to distinguish this condition from PLC [22]. Rarely, cases of progression of PLC to mycosis fungoides are reported. (See 'Association with malignancy' below and "Clinical manifestations, pathologic features, and diagnosis of mycosis fungoides".)

TREATMENT

Approach to treatment — Because pityriasis lichenoides chronica (PLC) is a benign, nonscarring condition that is often asymptomatic and self-limited, treatment is not mandatory. However, we find that many patients desire therapy to improve the visible signs of the disease.

The best approach to treatment is unclear due to a paucity of high-quality efficacy data. Sources of data are primarily limited to case reports and retrospective studies [24]. Moreover, many studies have combined outcome data from patients with PLC and pityriasis lichenoides et varioliformis acuta (PLEVA), complicating interpretation of treatment efficacy for patients with PLC.

Given the lack of high-quality data on treatment efficacy and the benign course of PLC, the risks associated with pursuing treatment should always be considered carefully. Our initial approach to treatment consists of therapies that have been reported to be effective and have a favorable safety profile. We favor topical corticosteroids, oral antibiotics with anti-inflammatory properties, and ultraviolet B (UVB) phototherapy for first-line therapy for PLC. Because of concern for serious drug side effects, we reserve treatment with methotrexate and other systemic immunomodulatory therapies for patients with severe and refractory disease.

First-line therapy — Topical corticosteroids, oral antibiotics, and phototherapy are our first-line treatments for PLC.

Topical corticosteroids — Topical corticosteroids are commonly used for PLC despite few published data on their efficacy. These agents may be useful for improving inflammation and reducing associated pruritus. In a retrospective review that included 18 adults and 16 children with PLEVA or PLC who received topical corticosteroid therapy, approximately one-half found the treatment useful for clearing or virtually clearing symptoms or signs of the disease [3]. We typically prescribe a medium-potency topical corticosteroid (eg, triamcinolone 0.1% cream) to be applied twice daily for four to six weeks to sites of active lesions.

Cutaneous atrophy is a potential adverse effect of topical corticosteroid use that is most likely to occur with long-term use of high-potency corticosteroids. Additional side effects of topical corticosteroids, including the effects of systemic absorption, are reviewed separately. (See "Topical corticosteroids: Use and adverse effects", section on 'Adverse effects'.)

Oral antibiotics — Oral antibiotics with anti-inflammatory properties may be useful for the management of PLC and are commonly used as first-line therapy. In particular, patients with widespread eruptions may prefer oral therapy over topical therapy due to the difficulty of applying a topical agent to multiple areas.

Tetracyclines and erythromycin are the oral antibiotics most commonly used for PLC. Tetracyclines are typically used for the treatment of adolescents and adults. Tetracyclines should not be given to children under the age of nine or pregnant women due to the risk for permanent discoloration of developing teeth. Thus, erythromycin is typically used for the treatment of children with PLC.

Improvement with oral antibiotic therapy is usually evident within the first several weeks of treatment. If benefit is not evident within three months, we discontinue the oral antibiotic and consider initiating phototherapy.

Tetracyclines — The efficacy of tetracycline was evaluated in an uncontrolled study of 13 patients with pityriasis lichenoides (subtype unspecified) [25]. Patients were treated with 2 g per day of tetracycline until lesions subsided followed by 1 g per day for one month. Of the 13 patients, 12 achieved marked improvement within four weeks. Seven patients needed to continue tetracycline (1 g per day) to maintain the response to treatment.

Favorable results following treatment with a tetracycline class antibiotic were also reported in a separate retrospective study. Three of four adults treated for pityriasis lichenoides (subtype unspecified) with minocycline (100 mg twice daily for eight weeks) achieved clearance or near clearance of skin lesions [3].

Our typical regimen of tetracyclines for adults consists of one of the following:

●Doxycycline (200 mg per day in two divided doses)

●Minocycline (200 mg per day in two divided doses)

●Tetracycline (2000 mg per day in four divided doses)

Gastrointestinal distress is a potential side effect of these antibiotics. In addition, tetracyclines (particularly tetracycline and doxycycline) may induce photosensitivity. Uncommon side effects of minocycline include skin pigmentation and a lupus-like syndrome.

Erythromycin — The findings of several retrospective studies in children with pityriasis lichenoides suggest that oral erythromycin may be beneficial in this population [4,5,7,26]. Most studies have not separated outcomes for patients with PLC from those with PLEVA:

●In a retrospective study that included 124 children with pityriasis lichenoides (71 PLEVA, 46 PLC, 7 with features of both disorders), 67 percent of 57 children treated with oral erythromycin (30 to 50 mg/kg per day) appeared to respond to treatment [4]. The mean time to response was two months. Among those who improved, 61 percent had complete clearance of skin lesions.

●In a retrospective study of 22 children with pityriasis lichenoides (14 PLEVA, 8 PLC), 11 of 15 children who were treated with erythromycin (varying doses) and were available for follow-up achieved clinical remission (73 percent) [7]. Remission was generally achieved within two months, and 7 of the 11 patients were able to discontinue therapy and remained free of lesions during follow-up periods ranging from six weeks to three years. Four patients who did not receive erythromycin appeared to have slower rates of improvement.

However, not all studies have yielded a high rate of response. A retrospective study of eight children with pityriasis lichenoides (type unspecified) treated with erythromycin (40 to 60 mg/kg per day) found that only two children achieved clearance after three months of treatment, one of whom relapsed within four weeks of treatment cessation [3].

The dose of erythromycin that we typically use for children is 30 to 50 mg/kg per day. Gastrointestinal distress is a potential side effect of erythromycin therapy.

Azithromycin, another macrolide antibiotic, has been reported to be effective in a few patients with PLEVA [27-30]. The efficacy of azithromycin for PLC is unclear. (See "Pityriasis lichenoides et varioliformis acuta (PLEVA)", section on 'Azithromycin'.)

Phototherapy — Phototherapy is a well-tolerated modality that is often beneficial for PLC. Phototherapy is easily administered to a wide area of skin, a favorable feature for patients with widespread involvement. However, the multiple office visits required make phototherapy a less feasible treatment option for some patients. Narrowband ultraviolet B (NBUVB), broadband UVB, and psoralen plus ultraviolet A (PUVA) are the primary phototherapeutic modalities used to treat these diseases. We favor use of UVB phototherapy based upon the more favorable safety profile compared with PUVA photochemotherapy. (See "UVB therapy (broadband and narrowband)" and "Psoralen plus ultraviolet A (PUVA) photochemotherapy".)

Efficacy — Several uncontrolled and retrospective studies have evaluated the efficacy of UVB phototherapy for PLC in children and/or adults [31-38], with most studies reporting improvement in the majority of patients. One of the largest retrospective studies of NBUVB phototherapy in patients with PLC (n = 25, Fitzpatrick skin phototype II or III (table 1)) documented complete (>75 percent improvement) and partial (50 to 75 percent improvement) responses in 48 and 44 percent of patients, respectively [32]. In a separate retrospective study that included eight patients with PLC (Fitzpatrick skin phototype I or II) who were treated with NBUVB, seven (88 percent) achieved a complete response (at least 90 percent clearance of skin lesions) and one patient achieved a partial response (50 to 89 percent clearance of lesions) [31]. In a retrospective study that included nine patients with PLC treated with phototherapy, four patients (44 percent) reported at least 76 percent improvement in cutaneous lesions [38].

Few studies have directly compared the efficacy of different forms of phototherapy for PLC. Similar efficacy of NBUVB and PUVA was suggested by an unblinded trial in which 15 patients with PLC were randomly assigned to either treatment [39]. The trial did not find a significant difference in the rate of response to therapy; 88 percent of NBUVB-treated patients and 74 percent of PUVA-treated patients achieved more than 90 percent resolution of papulosquamous and plaque lesions, and the mean number of treatment sessions required to achieve this response was similar. In addition, a retrospective study that compared NBUVB with broadband UVB therapy in 29 patients with pityriasis lichenoides (PLEVA, PLC, or an overlap syndrome) found a similar rate of response [34]. Complete clearance of lesions was achieved by 93 percent of patients in both groups.

Ultraviolet A1 (UVA1) phototherapy is not widely available and experience with this modality for PLC is limited. In a prospective study, treatment with UVA1 was associated with complete clinical and histologic improvement in six of eight patients with PLC or PLEVA [40].

Administration — At least two to three months of treatment is usually required to achieve good responses to UVB and PUVA phototherapy. Treatment often is initially administered at least three times weekly and tapered to less frequent treatments once there is a satisfactory response. Relapse may occur after the discontinuation of treatment. In a retrospective study in which seven of eight adults with PLC refractory to topical therapy responded to NBUVB therapy, three patients relapsed within three months after treatment cessation, suggesting that some patients may require long-term maintenance therapy [37].

Potential adverse effects of UVB and PUVA phototherapy include blistering, burns, and pruritus. Increased risk for squamous cell carcinoma has been reported in psoriasis patients who have received high numbers of PUVA treatments [41]. The adverse effects of phototherapy are reviewed in greater detail separately. (See "UVB therapy (broadband and narrowband)", section on 'Short- and long-term adverse effects' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Adverse effects'.)

Second-line therapies — There are few data on additional treatment options for PLC.

Topical tacrolimus — A few case reports suggest that topical tacrolimus may be an additional topical treatment option for pityriasis lichenoides. Improvement of longstanding PLC that failed to respond sufficiently to topical clobetasol, oral erythromycin, phototherapy, or methotrexate was documented in a patient in whom lesions on one side of the body were treated with tacrolimus 0.1% ointment twice daily [42]. Although marked improvement was noted within two weeks, lesions recurred soon after treatment cessation. Topical tacrolimus also appeared to be useful in two children with PLEVA [43]. Additional studies will be useful for confirming the efficacy of topical tacrolimus for PLC.

Transient stinging or burning sensations may occur at sites of tacrolimus application. Although some safety concerns have been raised regarding the risk for lymphoma in patients treated with topical tacrolimus, a causative relationship has not been proven. (See "Treatment of atopic dermatitis (eczema)", section on 'Safety'.)

Methotrexate — Case reports have documented efficacy of methotrexate treatment in a few patients with PLC, including patients with PLC that appeared to be induced by treatment with a biologic tumor necrosis factor (TNF)-alpha inhibitor [16,44,45]. Methotrexate has also been used successfully for the treatment of PLEVA and febrile ulceronecrotic Mucha-Habermann disease (FUMHD). (See "Pityriasis lichenoides et varioliformis acuta (PLEVA)", section on 'Refractory disease'.)

Due to the benign clinical course of PLC and the potential side effects of methotrexate, our use of methotrexate is infrequent. We primarily reserve methotrexate therapy for patients with extensive or symptomatic PLC who have failed other therapies. The side effects of methotrexate are reviewed separately. (See "Major side effects of low-dose methotrexate".)

Other — Treatment with other systemic therapies, such as dapsone, acitretin with PUVA, systemic glucocorticoids, cyclosporine, and intravenous immunoglobulin, have been suggested for the treatment of refractory PLEVA or FUMHD based upon isolated reports of benefit [2,46-49]. The efficacy of these agents in PLC is unclear. The risks of treatment should be carefully considered prior to attempting treatment with such agents. A response to photodynamic therapy has been reported in one patient with PLC [50].

ASSOCIATION WITH MALIGNANCY — The development of cutaneous lymphoma, most commonly mycosis fungoides, has been reported in several children and adults with pityriasis lichenoides chronica (PLC) [13,51-55]. In addition, two patients in whom PLC appeared to be a paraneoplastic phenomenon related to a renal oncocytoma or an extranodal lymphoma have been reported [54,56]. (See "Clinical manifestations, pathologic features, and diagnosis of mycosis fungoides", section on 'Clinical features'.)

Given the apparent rarity of associations between PLC and malignancy, PLC is considered a benign disease. However, as a precaution, we perform a full skin examination on patients with PLC at least once yearly to evaluate for signs of cutaneous lymphoma. We also encourage patients to return if atypical skin lesions develop (eg, persistent inflammatory patches, plaques, or tumor-like nodules). We do not routinely perform cancer screening beyond recommended age-appropriate measures.

SUMMARY AND RECOMMENDATIONS

●Pityriasis lichenoides chronica (PLC) is a rare inflammatory skin disorder of unknown etiology that is considered a subtype of pityriasis lichenoides. PLC most commonly occurs in young adults and children. (See 'Epidemiology' above.)

●Patients with PLC usually present with widely distributed, red-brown papules on the trunk and extremities (picture 1A-C). A mica-like scale overlying the papules often is visible. Most patients are asymptomatic. Occasionally, associated pruritus is present. (See 'Clinical features' above.)

●Although PLC has a relapsing and remitting course that persists for months to years, individual lesions tend to resolve within a few weeks. Hypopigmented macules or patches often remain at the sites of prior lesions. (See 'Clinical features' above.)

●A diagnosis of PLC is suspected based upon the findings on the physical examination. A skin biopsy is usually performed to confirm the diagnosis. (See 'Diagnosis' above.)

●Because PLC is a benign, often asymptomatic and self-limited disorder, treatment is not mandatory. However, many patients desire treatment to improve the appearance of skin lesions. (See 'Approach to treatment' above.)

●Data on the efficacy of treatments for PLC are limited. For patients with PLC who desire treatment, we suggest the use of topical corticosteroids, oral antibiotics (tetracyclines for adults and erythromycin for children), or ultraviolet B (UVB) phototherapy as initial treatment due to the relative safety of these interventions (Grade 2C). (See 'First-line therapy' above.)

●Although PLC is considered a benign disorder, infrequent reports have linked PLC to the development of cutaneous lymphoma. As a precaution, we perform skin examinations in patients with PLC at least once yearly. (See 'Association with malignancy' above.)