ﺑﺎﺯﮔﺸﺖ ﺑﻪ ﺻﻔﺤﻪ ﻗﺒﻠﯽ
خرید پکیج
تعداد آیتم قابل مشاهده باقیمانده : 3 مورد
نسخه الکترونیک
medimedia.ir

Pityriasis lichenoides et varioliformis acuta (PLEVA)

Pityriasis lichenoides et varioliformis acuta (PLEVA)
Literature review current through: Jan 2024.
This topic last updated: Aug 13, 2021.

INTRODUCTION — Pityriasis lichenoides et varioliformis acuta (PLEVA), otherwise known as Mucha-Habermann disease, is an uncommon cutaneous inflammatory disorder that most frequently affects young adults and children. PLEVA usually presents as an acute eruption of inflammatory papules and papulovesicles that rapidly develop hemorrhagic or necrotic crusts (picture 1A-C). Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a potentially life-threatening, severe presentation of PLEVA.

Pityriasis lichenoides chronica (PLC), which is characterized by the appearance of multiple scaly, red-brown papules on the skin, is often considered to be on a disease continuum with PLEVA (picture 2) [1]. The term "pityriasis lichenoides" is frequently used to refer to the spectrum of these disorders.

The clinical features, diagnosis, and management of PLEVA will be discussed here. PLC is reviewed separately. (See "Pityriasis lichenoides chronica".)

EPIDEMIOLOGY — PLEVA is a rare disorder. The precise incidence and prevalence are not known. PLEVA may occur at any age (including infants) [2] but most frequently occurs in children and young adults.

Data on PLEVA and pityriasis lichenoides chronica (PLC) are often combined in the literature under pityriasis lichenoides, complicating the assessment of the epidemiology of PLEVA. A slight male predominance has been detected among children with pityriasis lichenoides [1], and in one of the largest series of children with pityriasis lichenoides, 40 of 71 children with PLEVA (56 percent) were male [3]. A male predominance is less consistently observed in the general population of patients with pityriasis lichenoides [1].

Similar to the classic presentation of PLEVA, the severe febrile ulceronecrotic Mucha-Habermann disease (FUMHD) variant primarily occurs in children and young adults. A 2008 review of 40 reported cases found that the mean age of affected patients was 27 (range 4 to 82 years) [4]. The majority of patients (75 percent) were under the age of 35 years.

Ethnic or geographic differences in the prevalence of PLEVA and FUMHD have not been definitively established.

PATHOGENESIS — The pathogenesis of PLEVA is poorly understood. The two prevailing pathogenic theories involve the classification of PLEVA as a T cell dyscrasia and the designation of PLEVA as an aberrant immune response to viral, bacterial, or protozoal infections.

The identification of T cell clones in patients with PLEVA, the clinical resemblance of PLEVA to lymphomatoid papulosis, and the rare development of lymphoma in patients with PLEVA are used to support the concept that PLEVA and febrile ulceronecrotic Mucha-Habermann disease (FUMHD) may be T cell lymphoproliferative disorders [5-7]. In one study of patients with PLEVA, a dominant T cell clone was detected in 13 of 20 biopsy specimens [6] Based upon this theory, an immune response that attacks and eventually eliminates the T cell clone could account for the self-limited disease course that typically characterizes PLEVA. (See 'Disease course' below.)

The assertion that PLEVA represents a hypersensitivity reaction to infectious agents arises from multiple reports of the development of PLEVA in the setting of recent or concurrent infections. Examples include infections due to Toxoplasma gondii, human herpesvirus 8, Epstein-Barr virus, HIV, varicella-zoster virus, and group A Streptococcus [8-14]. In accordance with the infection theory, the detection of T cell clones in PLEVA could represent a clonal immunologic response to a microbial antigen, rather than a primary lymphoproliferative disease. Case reports describing the development of PLEVA soon after receipt of a live-attenuated measles vaccine; the combined measles, mumps, and rubella vaccine; influenza; and tetanus vaccination may provide additional support for this theory [15-18]. There are also reports of PLEVA following immunomodulatory medications, such as pembrolizumab and diphenylcyclopropenone [19,20].

In addition, plasmacytoid dendritic cells, which produce type I interferons and play a key role in defense against viral infections, have been found in specimens from lesions of pityriasis lichenoides chronica (PLC) and PLEVA [21].

An interesting observation is the detection of elevated levels of the proinflammatory cytokine tumor necrosis factor (TNF)-alpha and the soluble interleukin (IL) 2 receptor (a marker of elevated T cell activation) in patients with FUMHD [5,22,23]. The relevance of these findings in the pathogenesis of FUMHD remains to be determined. Although successful therapy with infliximab (a biologic TNF-alpha inhibitor) has been documented in case reports [24,25], there are also case reports describing PLC induced by the biologic TNF-alpha inhibitors adalimumab and etanercept [26,27].

Several exogenously administered substances have been linked to the development of features consistent with PLEVA in case reports, such as tegafur, astemizole, estrogen-progesterone, and radiocontrast iodide [28-31]. The mechanisms by which these substances might induce PLEVA are unknown.

CLINICAL MANIFESTATIONS

PLEVA — PLEVA usually begins as an acute eruption of multiple erythematous macules that rapidly evolve to form 3 to 15 mm inflammatory papules and papulovesicles, some of which develop hemorrhagic or necrotic crusts (picture 1A-C). Although the trunk, proximal extremities, and skin flexures are the most common sites for involvement, any cutaneous surface may be affected [32]. Mucosal involvement is typically absent.

The individual skin lesions of PLEVA usually appear and resolve over the course of a few weeks [33]. However, new lesions often develop as earlier lesions resolve, resulting in ongoing disease and the simultaneous presence of lesions in various stages of development. Hypopigmentation and hyperpigmentation frequently persist after lesion resolution (picture 1C) [3]. Scarring may or may not develop.

The cutaneous lesions of PLEVA may be asymptomatic, pruritic, or associated with a burning sensation [32,34]. Systemic symptoms are often absent, but in a minority of patients, fevers or arthralgias occur [3].

Occasionally, patients experience infectious symptoms prior to the onset of the skin eruption. In one retrospective series that included 71 children with PLEVA, 46 children with pityriasis lichenoides chronica (PLC), and 7 children with manifestations of both conditions, an infection (most commonly an upper respiratory infection) preceded the onset of skin disease in 28 children (23 percent) [3].

The term "PLEVA pemphigoides" has been used to refer to a rare variant characterized by typical PLEVA lesions that progress to bullae associated with bullous pemphigoid antigen 180 (BP180) antibodies [35].

Febrile ulceronecrotic Mucha-Habermann disease — Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) may occur de novo or in the setting of preexisting PLEVA [4]. Compared with PLEVA, the clinical manifestations of FUMHD are more severe. Affected patients develop an acute eruption of necrotic papules that rapidly evolve to form necrotic plaques and ulcers that reach up to a few centimeters in diameter (picture 3) [33]. Hemorrhagic bullae and oral, genital, and conjunctival mucosal ulcerations may also occur [1]. The skin lesions often resolve with atrophic scarring [1].

The cutaneous findings of FUMHD are accompanied by persistent high fevers (up to 40°C) and fatigue. Internal involvement is common, and may manifest as cardiomyopathy, central nervous system vasculitis, arthritis, interstitial pneumonitis, hematologic abnormalities, abdominal pain, diarrhea, sepsis, or other disorders [5,22,36-39].

DISEASE COURSE — PLEVA often follows a relapsing and remitting course prior to spontaneous resolution, and periods of complete or near complete remission may be interspersed with periods of greater disease activity. The duration of PLEVA prior to resolution is highly variable, ranging from a few weeks to years. As an example, a retrospective study that included 71 children with PLEVA found a median duration of PLEVA of 18 months (range 4 to 108 months), and a study that included 22 children and adults with PLEVA found a median disease duration of 24 months (range 2 to 132 months) [3,40]. In contrast, a retrospective study that included five patients with PLEVA and one patient with febrile ulceronecrotic Mucha-Habermann disease (FUMHD) found an average duration of disease of only 1.6 months [41].

During the course of PLEVA, patients can develop scaly, red-brown papules that are consistent with pityriasis lichenoides chronica (PLC) alongside lesions consistent with PLEVA, and occasionally, patients completely transition from PLEVA to PLC [42]. These observations have been used to support the concept that PLEVA and PLC represent a spectrum of a single disease. (See 'Differential diagnosis' below.)

FUMHD is a serious and potentially fatal disease. A 2008 review found that 9 of 40 reported cases (15 children and 25 adults) resulted in death [4]. All deaths occurred in adults. FUMHD usually does not recur [39].

DIAGNOSIS — The recognition of consistent cutaneous findings raises suspicion for PLEVA. A skin biopsy is required to confirm the diagnosis and rule out other disorders that can closely resemble PLEVA.

Biopsy — The key histopathologic findings of PLEVA are found in the epidermis and dermis; thus, the biopsy specimen must adequately sample both of these structures. We typically obtain a tissue specimen via a 4 mm punch biopsy. Alternatively, an incisional biopsy can be performed. (See "Skin biopsy techniques", section on 'Biopsy site preparation'.)

In febrile ulceronecrotic Mucha-Habermann disease (FUMHD), the recognition of ulceration in the pathology specimen can assist with the interpretation of the biopsy findings. Therefore, in patients with suspected FUMHD, the biopsy specimen should include the edge of an ulcer.

Histopathology — The histologic findings of PLEVA are not pathognomonic, but when reviewed in conjunction with the clinical context, are valuable for diagnosis [3,43]. Typical histopathologic findings in PLEVA include [1]:

Parakeratosis, spongiosis, mild to moderate epidermal acanthosis

Vacuolar alteration of the basal layer

Exocytosis of lymphocytes and erythrocytes into the epidermis

Moderately dense, wedge-shaped lymphohistiocytic infiltrate extending from the papillary dermis into the deep reticular dermis

Additional findings that may be present include epidermal erosions or necrosis, vesiculation, endothelial swelling, dermal hemorrhage, and papillary dermal edema. Vasculitis is rare.

The histopathologic findings of FUMHD resemble the findings in PLEVA with a few exceptions [1]. The perivascular inflammatory infiltrate tends to be denser and necrosis is more prominent. In addition, leukocytoclastic vasculitis is a prominent feature in FUMHD.

Immunohistochemistry — Immunohistochemical studies can aid in confirming the diagnosis of PLEVA. The inflammatory infiltrate is usually primarily composed of CD8+ T lymphocytes. Unlike lymphomatoid papulosis (LyP), CD30 stains are usually negative [1]. (See "Lymphomatoid papulosis", section on 'Differential diagnosis' and "Lymphomatoid papulosis".)

Laboratory studies — No serologic tests are specific for the diagnosis of PLEVA. Leukocytosis and an elevated erythrocyte sedimentation rate or C-reactive protein level are common findings in FUMHD [44]. Depending on the extent and type of internal involvement, patients with FUMHD may exhibit a variety of other laboratory abnormalities. (See 'Febrile ulceronecrotic Mucha-Habermann disease' above.)

Based upon the reports of an association of PLEVA with infection, laboratory studies may be used to evaluate for evidence of existing or preceding infection if the clinical scenario suggests this possibility. Examples of the infections that are most frequently considered include group A Streptococcus, T. gondii, HIV, and Epstein-Barr virus infections [1]. (See 'Pathogenesis' above.)

DIFFERENTIAL DIAGNOSIS — Multiple inflammatory and infectious disorders share clinical features with PLEVA. Assessment of the clinical history, examination of the morphology and distribution of skin lesions, and review of the pathology findings facilitate the differentiation of PLEVA from these disorders.

Examples of disorders in the differential diagnosis of PLEVA are as follows:

Lymphomatoid papulosis Lymphomatoid papulosis (LyP) is the disease that most closely resembles PLEVA (table 1). Patients present with recurrent crops of inflammatory papules and small nodules that spontaneously regress, usually within several weeks (picture 4). Similar to PLEVA, crusted, hemorrhagic, and necrotic lesions may be present.

The histologic and immunohistochemical features of LyP differ from PLEVA and are useful for distinguishing between these diseases. LyP is characterized by a dermal infiltrate composed of large atypical lymphocytes that are CD30+ (picture 5). In contrast, atypical cells and CD30+ cells are few or absent in PLEVA. (See "Lymphomatoid papulosis".)

Pityriasis lichenoides chronica Pityriasis lichenoides chronica (PLC) is considered to be on a disease spectrum with PLEVA. Unlike PLEVA, which is characterized by the acute eruption of crusting and hemorrhagic papules, the lesions of PLC are usually red-brown papules with overlying micaceous scale that regress over the course of several weeks to months (picture 2) [33]. Of note, patients with PLEVA may simultaneously develop lesions consistent with PLC and occasionally transition to PLC from PLEVA [42]. (See "Pityriasis lichenoides chronica".)

Varicella – The acute development of papulovesicles on multiple areas of the skin is typical of varicella (picture 6). The lesions are often described as a dewdrop on a rose petal. Pruritus is usually present. The course of the disease is shorter than PLEVA, usually lasting only one to two weeks. Immunosuppressed patients may develop disseminated varicella, which presents with larger, hemorrhagic skin lesions and a longer disease course. Polymerase chain reaction or direct fluorescent antibody testing can be used to confirm the diagnosis. (See "Clinical features of varicella-zoster virus infection: Chickenpox" and "Diagnosis of varicella-zoster virus infection".)

Disseminated herpes simplex virus – In immunocompromised patients and patients who have a compromised skin barrier (eg, atopic dermatitis, Darier disease), herpes simplex virus infection may result in the development of widespread vesicles, pustules, and crusts (picture 7). The term "eczema herpeticum" is used to describe this occurrence in patients with atopic dermatitis. Polymerase chain reaction or direct fluorescent antibody testing can be used to identify herpes simplex infection. (See "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection", section on 'Eczema herpeticum' and "Epidemiology, clinical manifestations, and diagnosis of herpes simplex virus type 1 infection".)

Arthropod bites Multiple arthropod bites may result in the acute development of widespread, often pruritic, inflammatory papules (picture 8). Vesiculation and necrosis are infrequent findings. The patient history is useful for diagnosis. (See "Insect and other arthropod bites", section on 'Types of reactions'.)

Gianotti-Crosti syndrome Gianotti-Crosti syndrome is an uncommon disorder that usually occurs in young children. Children often have symptoms of an upper respiratory or gastrointestinal infection prior to the eruption of papules and papulovesicles primarily distributed on the face, buttocks, or extremities (picture 9). Hemorrhagic lesions may be present. Lymphadenopathy and hepatomegaly may accompany the cutaneous symptoms. The eruption typically resolves spontaneously within weeks to months. The morphology and distribution of lesions and biopsy findings can aid in distinguishing this disorder from PLEVA. (See "Gianotti-Crosti syndrome (papular acrodermatitis)".)

Langerhans cell histiocytosis In infants and young children, Langerhans cell histiocytosis (LCH) often presents with hemorrhagic papules (picture 10A-B). Unlike PLEVA, the eruption is primarily localized in seborrheic or intertriginous areas such as inguinal folds, axillae, scalp, and posterior auricular areas. A skin biopsy is useful for diagnosing LCH. (See "Clinical manifestations, pathologic features, and diagnosis of Langerhans cell histiocytosis", section on 'Skin and oral mucosa'.)

TREATMENT

Approach to treatment — Because PLEVA is a benign, usually self-limited disorder, clinical follow-up without pharmacologic treatment is an option for the management of children and adults with limited, nonscarring disease who are not bothered by the skin lesions. However, patients with extensive, persistent, symptomatic, scarring, or cosmetically disfiguring disease often desire treatment.

Due to the wide variation in the duration of PLEVA prior to spontaneous resolution, randomized trials to evaluate the treatments for PLEVA would be of value for confirming the effectiveness of interventions. However, PLEVA is a rare disorder, and data on the interventions for PLEVA are limited.

Antibiotic therapy with tetracyclines or erythromycin and phototherapy are considered first-line treatments based upon retrospective studies and case reports that suggest treatment benefit and the relatively low risk for severe adverse effects associated with these interventions. Both modalities often require two to three months of treatment to achieve satisfactory improvement, which may or may not persist after the discontinuation of therapy.

Data are insufficient to determine the comparative efficacy of oral antibiotics and phototherapy for PLEVA, and our decision of which modality to utilize as initial therapy primarily rests upon the consideration of patient characteristics and preferences. Factors such as comorbidities (eg, photosensitive disorders or melanoma), the cost and availability of phototherapy, and the multiple clinical visits required for phototherapy limit the use of phototherapy in some patients.

In children, we typically attempt treatment with oral antibiotic therapy prior to phototherapy due to the paucity of data on the long-term effects of phototherapy in children. Moreover, some children are unable to fully comply with the safety measures necessary for phototherapy.

Methotrexate is an additional treatment option that has appeared to be beneficial in individual patients with PLEVA. Due to concern regarding the adverse effects of this drug, we typically reserve methotrexate for patients who have failed oral antibiotics and phototherapy.

First-line therapies — First-line therapies for PLEVA include systemic antibiotics and phototherapy. Topical corticosteroids may be useful for improving symptoms.

Systemic antibiotics — Antibiotics with anti-inflammatory properties are the primary antibiotics utilized for PLEVA. Adolescents and adults are usually treated with tetracyclines. Tetracyclines are contraindicated in children under the age of nine due to deleterious effects on tooth development. Thus, erythromycin is typically utilized for antibiotic treatment in children.

Our typical treatment regimen for adults is as follows:

Doxycycline 100 mg once to twice daily

Minocycline 100 mg once to twice daily

Our typical treatment regimen for children is as follows:

Erythromycin 30 to 50 mg/kg per day given in two to four divided doses

We continue these doses until complete or almost complete lesion resolution is attained (typically within one to three months), then taper over one to two months as tolerated. Patients who relapse upon tapering or drug discontinuation can be given longer courses of therapy. If no response is evident after three months of treatment with an antibiotic, we discontinue treatment and consider phototherapy.

Azithromycin is an additional therapeutic option for children and adults, but experience with this drug in PLEVA is more limited. Data on the efficacy of specific antibiotics are provided below.

Tetracyclines — The use of tetracyclines in PLEVA is based upon an uncontrolled study that demonstrated efficacy of tetracycline in pityriasis lichenoides and case reports. In the uncontrolled study, 12 of 13 patients with pityriasis lichenoides who were treated with tetracycline (2 g per day until lesions subsided followed by 1 g per day for one month) had great improvement within four weeks [45]. The proportion of responders who had PLEVA or pityriasis lichenoides chronica (PLC) was not specified. However, the patient who failed to respond to treatment had features of PLEVA. Seven of the responders required the continuation of tetracycline (1 g per day) to maintain improvement.

Improvement following treatment with tetracyclines has been documented in individual reports of patients with PLEVA. Complete suppression of skin lesions occurred within three weeks in an adolescent girl treated with tetracycline (2 g per day) [46], and minocycline (100 mg per day) was associated with improvement in at least one of two patients with PLEVA in a retrospective series [34].

Erythromycin — Support for the use of erythromycin in PLEVA is derived from several retrospective studies, most of which combine patients with PLEVA and PLC [3,41,47,48]. Examples of studies in which the majority of patients had PLEVA include:

In a retrospective study that included 71 children with PLEVA, 46 children with PLC, and 7 children with a mixed presentation, 80 percent were treated with erythromycin (30 to 50 mg/kg per day) [3]. Among the 57 patients who were available for follow-up after treatment with erythromycin, 34 (67 percent) improved within a median of two months. Sixty-one percent of the responders achieved complete clearance of active skin lesions. The maintenance of the response after treatment cessation was not assessed.

In a retrospective study of 14 children with PLEVA and 8 children with PLC, 11 of 15 children who received erythromycin and were available for follow-up achieved remission (usually within two months). Seven children were able to discontinue erythromycin after two to five months of treatment and remained free of lesions for follow-up periods that ranged from six weeks to three years [47].

Less favorable results with erythromycin have been reported. In a case series in which eight children with PLEVA were treated with erythromycin for at least six weeks, two improved, four had no change in disease severity, and two worsened during treatment [49]. In addition, in a retrospective study in which eight children with pityriasis lichenoides (subtype unspecified) were treated with oral erythromycin, only two children had disease clearance after three months of treatment, one of whom relapsed within four weeks after treatment cessation [34].

Azithromycin — Azithromycin (500 mg for one day followed by 250 mg for four days taken on the first and third weeks of the month) was effective within one month for an adult woman with PLEVA who failed to respond to doxycycline and within two months in a child with PLEVA who did not improve with erythromycin [50]. A child treated with a combination of azithromycin and topical tacrolimus also seemed to benefit from treatment [51].

The potential adverse effects of azithromycin are reviewed separately. (See "Azithromycin and clarithromycin", section on 'Adverse reactions'.)

Phototherapy — Phototherapy with ultraviolet (UV) light is frequently utilized for the treatment of pityriasis lichenoides and appears to be effective in many patients with PLEVA [1,52]. The modalities utilized include narrowband ultraviolet B (NBUVB), broadband UVB, psoralen plus ultraviolet A (PUVA), and ultraviolet A1 (UVA1).

As noted above, comorbidities and the availability, feasibility, and cost of phototherapy are limiting factors for some patients. Phototherapy is usually administered at least three times weekly at the start of therapy and tapered after a satisfactory response. At least two to three months of treatment is usually required to achieve improvement. Similar to antibiotic therapy, relapses occur with variable frequency after the discontinuation of treatment.

The types of phototherapy that have been utilized in PLEVA are reviewed below:

Ultraviolet B – Ultraviolet B (UVB) is our first choice for phototherapy. The use of UVB phototherapy in pityriasis lichenoides is supported by retrospective studies and case series [52]. In a retrospective study that included 23 patients with PLEVA (all with skin phototypes I to III (table 2)) who were treated with NBUVB, 15 (65 percent) achieved at least 90 percent clearance of disease (mean number of treatments = 43, mean cumulative dose = 23 J/cm2) [52]. The remaining eight patients achieved partial responses (at least 50 to 90 percent clearance). Two of the complete responders relapsed within one year.

Either NBUVB or broadband UVB may be used for the treatment of PLEVA. A retrospective study of 29 patients with PLC, PLEVA, or an overlap syndrome did not find a significant difference in response rates to these modalities (93 percent in each treatment group responded) [53]. Additional studies are necessary to confirm whether differences in efficacy exist.

Psoralen plus ultraviolet A – Complete responses to psoralen plus ultraviolet A (PUVA) have been documented in multiple case reports, some of which demonstrated long-term clearance, and others in which recurrences appeared after treatment cessation [1]. However, in the absence of data that indicate superior efficacy of PUVA over UVB phototherapy, the need for the administration of a systemic photosensitizer and the potential for additional adverse effects related to the photosensitizing agent make PUVA a less favorable first-line option for phototherapy. (See "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Safety measures' and "Psoralen plus ultraviolet A (PUVA) photochemotherapy", section on 'Adverse effects'.)

Ultraviolet A1 – Data on the efficacy of ultraviolet A1 (UVA1) phototherapy are more limited than for UVB phototherapy. UVA1 phototherapy has been associated with complete responses in a few patients with PLEVA [54]. The availability of UVA1 is primarily restricted to academic centers, limiting the use of this therapy.

Continuing treatment at a reduced frequency (eg, tapering to once every two weeks) after a complete response is attained has been utilized by some clinicians, including ourselves, in an attempt to reduce the likelihood of recurrence [52,53]. The value of maintenance regimens has not been formally studied.

Outdoor sun exposure is sometimes tried for patients in whom phototherapy is not feasible. Patients are often instructed to expose the affected areas to midday sunlight for 10 to 20 minutes and to then slowly increase the duration of daily sun exposure to maintain tanned but not burned skin. The duration of sun exposure required is dependent on skin type (table 2). Patients with very fair skin who are unable to tan are not favorable candidates for this therapy.

The efficacy of outdoor sun exposure on PLEVA has not been formally evaluated. Our experience suggests that some patients achieve modest benefits. In temperate climates, this option is limited to the time period between late spring and early autumn.

Topical agents — Topical corticosteroids may be useful for attaining symptomatic relief or accelerating the resolution of individual lesions; however, these agents are not thought to alter the course of PLEVA. Medium or high potency topical corticosteroids are usually applied to individual lesions once or twice daily for two to three weeks (table 3). In a retrospective study, approximately half of 18 adults and 16 children treated with topical corticosteroids found these agents useful for alleviating disease signs and symptoms [34]. Case supports suggest that topical tacrolimus ointment may also be useful for PLEVA [51,55].

Refractory disease — Case reports indicate that methotrexate may be effective for PLEVA [49,56-58]. Methotrexate is administered once weekly at doses between 7.5 to 20 mg per week. In some patients, improvement has been noted within a few weeks.

Due to the potential for serious adverse effects related to methotrexate therapy, we typically reserve this treatment for patients who fail to respond to first-line therapies. Relapses during or after tapering of methotrexate appear to be common [56-58].

Other therapies that have been suggested for refractory disease include dapsone, acitretin, and cyclosporine [1]. Combination therapy with acitretin and PUVA was dramatically effective in two patients with refractory PLEVA within a few weeks [59].

Febrile ulceronecrotic Mucha-Habermann disease — Due to the rarity of febrile ulceronecrotic Mucha-Habermann disease (FUMHD) and the multiple therapies often administered simultaneously to these patients, the best approach to the treatment of FUMHD is unknown. Case reports document the use of a wide variety of therapeutic agents. Methotrexate appears to be the most consistently beneficial therapy [4]. Systemic glucocorticoids have been utilized in many reported cases, but whether they are truly beneficial remains unclear. Other agents that have been utilized for FUMHD include intravenous immunoglobulin, antibiotics, acyclovir, dapsone, cyclosporine, and phototherapy [39]. Inpatient management is usually required for these systemically ill patients.

Although elevated tumor necrosis factor (TNF)-alpha levels were detected in a child with FUMHD, a role for TNF-alpha inhibitors in FUMHD remains to be determined. There are case reports of successful therapy with infliximab [24,25]. In one report, only two doses were needed and lead to complete remission [25].

ASSOCIATION WITH LYMPHOMA — Rare reports of the development of cutaneous T cell lymphoma in patients with a history of PLEVA exist. Two children in whom this was thought to have occurred have been reported [60]. Pityriasis lichenoides chronica (PLC) has also been infrequently linked to cutaneous lymphoma [61,62]. (See "Pityriasis lichenoides chronica", section on 'Association with malignancy'.)

In light of the rarity of such reports, PLEVA is generally accepted as a disease with a benign clinical course. Signs that may suggest cutaneous lymphoma include the development of persistent cutaneous inflammatory patches or plaques or tumor-like nodules.

PATIENT FOLLOW-UP — Patients should be followed periodically (every three to six months) if treatment is deferred. This allows the clinician to discuss treatment if the disorder persists and provides the opportunity for reevaluation if the clinical findings evolve in a manner that suggests another diagnosis. We typically follow treated patients closely to monitor the effect of therapy.

SUMMARY AND RECOMMENDATIONS

PLEVA is an uncommon cutaneous disorder that is characterized by the acute development of inflammatory papules and papulovesicles with hemorrhagic or necrotic crusts on the skin (picture 1A-C). PLEVA may occur at any age, but children and young adults are most frequently affected. (See 'Epidemiology' above.)

The pathogenesis of PLEVA is not well understood. Theories on the pathogenesis of PLEVA include a view of PLEVA as a benign lymphoproliferative disorder or as a hypersensitivity response to infection. (See 'Pathogenesis' above.)

The cutaneous lesions of PLEVA tend to appear on the trunk, proximal extremities, and skin flexures. Although individual lesions often resolve within a few weeks, new crops of lesions often develop resulting in lesions at different stages of development. (See 'Clinical manifestations' above.)

PLEVA is a benign, self-limited disorder. However, symptoms may persist for weeks, months, or years. (See 'Disease course' above.)

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare, severe variant of PLEVA characterized by systemic illness, fever, and large ulcerated skin lesions. FUMHD can be fatal, particularly in adults. (See 'Febrile ulceronecrotic Mucha-Habermann disease' above and 'Disease course' above.)

The diagnosis of PLEVA is made through the assessment of clinical and histopathologic findings. The disorder that bears the closest clinical resemblance to PLEVA is lymphomatoid papulosis. A skin biopsy and immunohistochemical studies are useful for distinguishing between these diseases. (See 'Diagnosis' above and 'Differential diagnosis' above and "Lymphomatoid papulosis".)

Data are limited on the treatment options for PLEVA. Since the disease may be asymptomatic and self-limited, treatment is not always required. For adult patients who desire treatment, we suggest treatment with oral tetracyclines or ultraviolet B (UVB) phototherapy, based upon patient preferences and treatment availability (Grade 2C). For children with PLEVA we suggest treatment with oral erythromycin (Grade 2C). Children who fail to improve with oral erythromycin are candidates for UVB phototherapy if they can comply with therapy. (See 'Treatment' above.)

Methotrexate is a treatment option for PLEVA that is refractory to oral antibiotics and phototherapy. The risks and benefits of treatment with this agent should be considered carefully. (See 'Refractory disease' above.)

The best approach to treatment of FUMHD has not been established. Methotrexate and other systemic immunomodulators may be beneficial. Further study is necessary to determine the appropriate approach to the treatment of this disease. (See 'Febrile ulceronecrotic Mucha-Habermann disease' above.)

  1. Bowers S, Warshaw EM. Pityriasis lichenoides and its subtypes. J Am Acad Dermatol 2006; 55:557.
  2. Hoshina D, Akiyama M, Hamasaka K, Shimizu H. An infantile case of pityriasis lichenoides et varioliformis acuta. Br J Dermatol 2007; 157:194.
  3. Ersoy-Evans S, Greco MF, Mancini AJ, et al. Pityriasis lichenoides in childhood: a retrospective review of 124 patients. J Am Acad Dermatol 2007; 56:205.
  4. Sotiriou E, Patsatsi A, Tsorova C, et al. Febrile ulceronecrotic Mucha-Habermann disease: a case report and review of the literature. Acta Derm Venereol 2008; 88:350.
  5. Cozzio A, Hafner J, Kempf W, et al. Febrile ulceronecrotic Mucha-Habermann disease with clonality: a cutaneous T-cell lymphoma entity? J Am Acad Dermatol 2004; 51:1014.
  6. Dereure O, Levi E, Kadin ME. T-Cell clonality in pityriasis lichenoides et varioliformis acuta: a heteroduplex analysis of 20 cases. Arch Dermatol 2000; 136:1483.
  7. Weiss LM, Wood GS, Ellisen LW, et al. Clonal T-cell populations in pityriasis lichenoides et varioliformis acuta (Mucha-Habermann disease). Am J Pathol 1987; 126:417.
  8. Rongioletti F, Rivara G, Rebora A. Pityriasis lichenoides et varioliformis acuta and acquired toxoplasmosis. Dermatologica 1987; 175:41.
  9. Boss JM, Boxley JD, Summerly R, Sutton RN. The detection of Epstein Barr virus antibody in 'exanthematic' dermatoses with special reference to pityriasis lichenoides. A preliminary survey. Clin Exp Dermatol 1978; 3:51.
  10. Tomasini D, Tomasini CF, Cerri A, et al. Pityriasis lichenoides: a cytotoxic T-cell-mediated skin disorder. Evidence of human parvovirus B19 DNA in nine cases. J Cutan Pathol 2004; 31:531.
  11. English JC 3rd, Collins M, Bryant-Bruce C. Pityriasis lichenoides et varioliformis acuta and group-A beta hemolytic streptococcal infection. Int J Dermatol 1995; 34:642.
  12. Ostlere LS, Langtry JA, Branfoot AC, Staughton RC. HIV seropositivity in association with pityriasis lichenoides et varioliformis acuta. Clin Exp Dermatol 1992; 17:36.
  13. Smith JJ, Oliver GF. Febrile ulceronecrotic Mucha-Habermann disease associated with herpes simplex virus type 2. J Am Acad Dermatol 2009; 60:149.
  14. Longley J, Demar L, Feinstein RP, et al. Clinical and histologic features of pityriasis lichenoides et varioliformis acuta in children. Arch Dermatol 1987; 123:1335.
  15. Gunatheesan S, Ferguson J, Moosa Y. Pityriasis lichenoides et varioliformis acuta: a rare association with the measles, mumps and rubella vaccine. Australas J Dermatol 2012; 53:e76.
  16. Torinuki W. Mucha-Habermann disease in a child: possible association with measles vaccination. J Dermatol 1992; 19:253.
  17. Baykal L, Arıca DA, Yaylı S, et al. Pityriasis lichenoides et varioliformis acuta; Association with tetanus vaccination. J Clin Case Rep 2015; 5:518.
  18. Castro BA, Pereira JM, Meyer RL, et al. Pityriasis lichenoides et varioliformis acuta after influenza vaccine. An Bras Dermatol 2015; 90:181.
  19. Seong GH, Yun DK, Shon U, et al. A Case of Pityriasis Lichenoides et Varioliformis Acuta-Like Eruption Developed after Pembrolizumab Treatment for Invasive Thymoma. Ann Dermatol 2021; 33:94.
  20. Nam KH, Park SW, Jung ES, Lee SK. A case of pityriasis lichenoides et varioliformis acuta after topical application of diphenylcyclopropenone. Eur J Dermatol 2020; 30:317.
  21. Karouni M, Rahal JA, Kurban M, et al. Possible role of plasmacytoid dendritic cells in pityriasis lichenoides. Clin Exp Dermatol 2018; 43:404.
  22. Tsianakas A, Hoeger PH. Transition of pityriasis lichenoides et varioliformis acuta to febrile ulceronecrotic Mucha-Habermann disease is associated with elevated serum tumour necrosis factor-alpha. Br J Dermatol 2005; 152:794.
  23. Herron MD, Bohnsack JF, Vanderhooft SL. Septic, CD-30 positive febrile ulceronecrotic pityriasis lichenoides et varioliformis acuta. Pediatr Dermatol 2005; 22:360.
  24. Kreuter A, Knispel S, Wieland U, et al. Complete resolution of febrile ulceronecrotic Mucha-Habermann disease following infliximab therapy. J Dtsch Dermatol Ges 2016; 14:184.
  25. Meziane L, Caudron A, Dhaille F, et al. Febrile ulceronecrotic Mucha-Habermann disease: treatment with infliximab and intravenous immunoglobulins and review of the literature. Dermatology 2012; 225:344.
  26. Martínez-Peinado C, Galán-Gutiérrez M, Ruiz-Villaverde R, Solorzano-Mariscal R. Adalimumab-Induced Pityriasis Lichenoides Chronica That Responded Well to Methotrexate in a Patient With Psoriasis. Actas Dermosifiliogr 2016; 107:167.
  27. Echeverri AF, Vidal A, Cañas CA, et al. Etanercept-induced pityriasis lichenoides chronica in a patient with rheumatoid arthritis. Case Rep Dermatol Med 2015; 2015:168063.
  28. Kawamura K, Tsuji T, Kuwabara Y. Mucha-Habermann disease-like eruptions due to Tegafur. J Dermatol 1999; 26:164.
  29. Stosiek N, Peters KP, von den Driesch P. [Pityriasis-lichenoides-et-varioliformis-acuta-like drug exanthema caused by astemizole]. Hautarzt 1993; 44:235.
  30. Jowkar F, Namazi MR, Bahmani M, Monabati A. Triggering of pityriasis lichenoides et varioliformis acuta by radiocontrast iodide. J Dermatolog Treat 2008; 19:249.
  31. Hollander A, Grots IA. Mucha-Habermann disease following estrogen-progesterone therapy. Arch Dermatol 1973; 107:465.
  32. Khachemoune A, Blyumin ML. Pityriasis lichenoides: pathophysiology, classification, and treatment. Am J Clin Dermatol 2007; 8:29.
  33. Wood GS, Hu CH, Liu R. Parapsoriasis and pityriasis lichenoides. In: Fitzpatrick's Dermatology in General Medicine, 8th ed, Goldsmith LA, Katz SI, Gilchrest BA, et al. (Eds), McGraw Hill, 2012. Vol 1, p.285.
  34. Wahie S, Hiscutt E, Natarajan S, Taylor A. Pityriasis lichenoides: the differences between children and adults. Br J Dermatol 2007; 157:941.
  35. Reichel A, Grothaus J, Ott H. Pityriasis lichenoides acuta (PLEVA) pemphigoides: A rare bullous variant of PLEVA. Pediatr Dermatol 2020; 37:710.
  36. Rosman IS, Liang LC, Patil S, et al. Febrile ulceronecrotic Mucha-Habermann disease with central nervous system vasculitis. Pediatr Dermatol 2013; 30:90.
  37. Auster BI, Santa Cruz DJ, Eisen AZ. Febrile ulceronecrotic Mucha-Habermann's disease with interstitial pneumonitis. J Cutan Pathol 1979; 6:66.
  38. Luberti AA, Rabinowitz LG, Ververeli KO. Severe febrile Mucha-Habermann's disease in children: case report and review of the literature. Pediatr Dermatol 1991; 8:51.
  39. Perrin BS, Yan AC, Treat JR. Febrile ulceronecrotic Mucha-Habermann disease in a 34-month-old boy: a case report and review of the literature. Pediatr Dermatol 2012; 29:53.
  40. Zang JB, Coates SJ, Huang J, et al. Pityriasis lichenoides: Long-term follow-up study. Pediatr Dermatol 2018; 35:213.
  41. Romaní J, Puig L, Fernández-Figueras MT, de Moragas JM. Pityriasis lichenoides in children: clinicopathologic review of 22 patients. Pediatr Dermatol 1998; 15:1.
  42. Fernandes NF, Rozdeba PJ, Schwartz RA, et al. Pityriasis lichenoides et varioliformis acuta: a disease spectrum. Int J Dermatol 2010; 49:257.
  43. Hood AF, Mark EJ. Histopathologic diagnosis of pityriasis lichenoides et varioliformis acuta and its clinical correlation. Arch Dermatol 1982; 118:478.
  44. Ito N, Ohshima A, Hashizume H, et al. Febrile ulceronecrotic Mucha-Habermann's disease managed with methylprednisolone semipulse and subsequent methotrexate therapies. J Am Acad Dermatol 2003; 49:1142.
  45. Piamphongsant T. Tetracycline for the treatment of pityriasis lichenoides. Br J Dermatol 1974; 91:319.
  46. Shelley WB, Griffith RF. Pityriasis lichennoides et varioliformis acuta. A report of a case controlled by a high dose of tetracycline. Arch Dermatol 1969; 100:596.
  47. Truhan AP, Hebert AA, Esterly NB. Pityriasis lichenoides in children: therapeutic response to erythromycin. J Am Acad Dermatol 1986; 15:66.
  48. Hapa A, Ersoy-Evans S, Karaduman A. Childhood pityriasis lichenoides and oral erythromycin. Pediatr Dermatol 2012; 29:719.
  49. Rasmussen JE. Mucha-Habermann's disease. Arch Dermatol 1979; 115:676.
  50. Skinner RB, Levy AL. Rapid resolution of pityriasis lichenoides et varioliformis acuta with azithromycin. J Am Acad Dermatol 2008; 58:524.
  51. Di Costanzo L, Balato N, La Bella S, Balato A. Successful association in the treatment of pityriasis lichenoides et varioliformis acuta. J Eur Acad Dermatol Venereol 2009; 23:971.
  52. Aydogan K, Saricaoglu H, Turan H. Narrowband UVB (311 nm, TL01) phototherapy for pityriasis lichenoides. Photodermatol Photoimmunol Photomed 2008; 24:128.
  53. Pavlotsky F, Baum S, Barzilai A, et al. UVB therapy of pityriasis lichenoides--our experience with 29 patients. J Eur Acad Dermatol Venereol 2006; 20:542.
  54. Pinton PC, Capezzera R, Zane C, De Panfilis G. Medium-dose ultraviolet A1 therapy for pityriasis lichenoides et varioliformis acuta and pityriasis lichenoides chronica. J Am Acad Dermatol 2002; 47:410.
  55. Simon D, Boudny C, Nievergelt H, et al. Successful treatment of pityriasis lichenoides with topical tacrolimus. Br J Dermatol 2004; 150:1033.
  56. Lynch PJ, Saied NK. Methotrexate treatment of pityriasis lichenoides and lymphomatoid papulosis. Cutis 1979; 23:634.
  57. Cornelison RL Jr, Knox JM, Everett MA. Methotrexate for the treatment of Mucha-Habermann disease. Arch Dermatol 1972; 106:507.
  58. Lazaridou E, Fotiadou C, Tsorova C, et al. Resistant pityriasis lichenoides et varioliformis acuta in a 3-year-old boy: successful treatment with methotrexate. Int J Dermatol 2010; 49:215.
  59. Pansé I, Bourrat E, Rybojad M, Morel P. [Photochemotherapy for pityriasis lichenoides: 3 cases]. Ann Dermatol Venereol 2004; 131:201.
  60. Fortson JS, Schroeter AL, Esterly NB. Cutaneous T-cell lymphoma (parapsoriasis en plaque). An association with pityriasis lichenoides et varioliformis acuta in young children. Arch Dermatol 1990; 126:1449.
  61. Thomson KF, Whittaker SJ, Russell-Jones R, Charles-Holmes R. Childhood cutaneous T-cell lymphoma in association with pityriasis lichenoides chronica. Br J Dermatol 1999; 141:1146.
  62. Panizzon RG, Speich R, Dazzi H. Atypical manifestations of pityriasis lichenoides chronica: development into paraneoplasia and non-Hodgkin lymphomas of the skin. Dermatology 1992; 184:65.
Topic 15282 Version 12.0

References

آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟