pityriasis lichenoides

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Media file 1: Typical hemorrhagic crusted papules of pityriasis lichenoides et varioliformis acuta.

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Media file 2: Close-up view of typical lesions of pityriasis lichenoides et varioliformis acuta.

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Media file 3: Scaling papules of pityriasis lichenoides chronica.

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Pityriasis Lichenoides

Follow-up

Further Outpatient Care

Patients with a waxing and waning course of Mucha-Habermann disease require follow-up monitoring and additional treatment depending on the severity of the disease.

Regarding the questionable potential for malignant transformation, some authors have suggested that follow-up biopsy should be performed on lesions that last longer than 1 year and are refractory to treatment.

Deterrence/Prevention

No preventive methods have been identified.

Complications

Ulceronecrotic pityriasis lichenoides et varioliformis acuta (PLEVA) can lead to scarring.

Prognosis

No clear consensus has been formed regarding duration of the disease, but most cases tend to resolve over time.

Miscellaneous

Medicolegal Pitfalls

A diagnosis of lymphomatoid papulosis should not be missed because of the theoretical possibility of subsequent development of a myeloproliferative disorder. Biopsies should be obtained to confirm a diagnosis of PLEVA.

Patients must be told that lesions may take time to resolve and that the duration of the disease cannot be predicted.

pityriasis lichenoides

Treatment

Medical Care

Large ulcerations found in the febrile ulceronecrotic variant of pityriasis lichenoides et varioliformis acuta (PLEVA) require local wound care. Infected lesions may be treated with topical mupirocin and sterile dressing changes twice daily.

No randomized controlled trials of the use of medications have been performed in Mucha-Habermann disease. Since the disease tends towards self-resolution, evaluation of treatments without adequate controls cannot result in useful recommendations. A number of open trials have reported success with light therapy and oral medications.²⁰

Medication

No randomized controlled trials have been performed in Mucha-Habermann disease. Since the disease course tends towards self-resolution, evaluation of treatments without adequate controls cannot result in rational recommendations. Nevertheless, a number of open trials have reported success with light therapy and oral medications.

Phototherapy has been reported useful in the treatment of subacute or chronic disease.²¹ Psoralen plus UV-A (PUVA) therapy (150-200 J/cm²) has been reported, with as many as 4 treatments per week to a total of 30-35 treatments, depending on the patient's skin type. UV-A without psoralens and UV-B may result in clearing. Relapses are not uncommon. Narrow-band ultraviolet B phototherapy and photodynamic therapy have also been reported as effective.^22,23,24,25

Case reports suggest the use of multiple oral medications including tetracycline,¹⁸ azithromycin, erythromycin, sulfonamides, dapsone, chloroquine, streptomycin, isoniazid, penicillin, methotrexate (MTX),²⁶ etretinate, and pentoxifylline. Potent topical corticosteroids may be useful if few lesions are present. Systemic corticosteroids may have a role in severe cases of PLEVA. Despite a lack of randomized controlled trials, oral tetracycline and erythromycin have been prescribed most often in case series.

Antibiotics

May have immunomodulatory activity. Empiric antimicrobial therapy must be comprehensive and should cover all likely pathogens in the context of the clinical setting.

Tetracycline (Sumycin)

Treats gram-positive and gram-negative organisms, as well as mycoplasmal, chlamydial, and rickettsial infections. Inhibits bacterial protein synthesis by binding with 30S and possibly 50S ribosomal subunit(s).

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

1-2 g PO divided bid/qid

Pediatric

£ 8 years: Not recommended
>8 years: 25-50 mg/kg PO divided bid/qid

Erythromycin (E.E.S., E-Mycin, Ery-Tab)

Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes causing RNA-dependent protein synthesis to arrest. For treatment of staphylococcal and streptococcal infections.
In children, age, weight, and severity of infection determine proper dosage. When bid dosing is desired, half-total daily dose may be administered q12h. For more severe infections, dose is doubled.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

250 mg PO qid or 333 mg PO q8h

Pediatric

30-50 mg/kg/d PO in divided doses

Psoralens

Tricyclic furocoumarins, when combined with UV radiation, produce DNA photoproducts resulting in suppression of both DNA synthesis and cell division.

Methoxsalen (Oxsoralen-Ultra, 8-MOP)

Inhibits mitosis by binding covalently to pyrimidine bases in DNA when photoactivated by UV-A.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

0.57 mg/kg PO 1.5-2 h before exposure to UV light; treatments should be at least 48 h apart

Pediatric

Not established

Retinoids

Regulate cell growth and proliferation.

Acitretin (Soriatane)

Retinoic acid analog, similar to etretinate and isotretinoin. Etretinate is main metabolite and has demonstrated clinical effects close to those seen with etretinate. Mechanism of action is unknown.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

0.75-1 mg/kg/d PO in divided doses; increase at weekly intervals by 0.25 mg/kg/d up to 1.5 mg/kg/d; establish maintenance dose (0.5-0.75 mg/kg/d) after 8-10 wk of therapy

Pediatric

Not established

Antimetabolites

MTX inhibits dihydrofolate reductase, thereby hindering DNA synthesis and cell reproduction.

Methotrexate (Folex, Rheumatrex)

May suppress immune system. Ameliorates symptoms of inflammation (eg, pain, swelling, stiffness).
Satisfactory response seen in 3-6 wk following administration. Adjust dose gradually to attain satisfactory response.

• Dosing
• Interactions
• Contraindications
• Precautions

Adult

0.3 mg/kg/wk PO/IM; not to exceed 20 mg

Pediatric

5-15 mg/m²/wk PO/IM qd or divided tid administered 12 h apart

Pityriasis Lichenoides

Author: Peter A Klein, MD, Residency Program Director, Department of Dermatology, University Hospital, State University of New York at Stony Brook
Coauthor(s): Jeffrey P Callen, MD, Professor of Medicine (Dermatology), Chief, Division of Dermatology, University of Louisville School of Medicine
Contributor Information and Disclosures

Updated: Jul 12, 2010

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• Overview
• Differential Diagnoses & Workup
• Treatment & Medication
• Follow-up
• Multimedia

• References
• Keywords

Introduction

Background

Pityriasis lichenoides is a rare cutaneous disorder of unknown etiology. Pityriasis lichenoides encompasses a spectrum of clinical presentations ranging from acute papular lesions that rapidly evolve into pseudovesicles and central necrosis (pityriasis lichenoides et varioliformis acuta or PLEVA) to small, scaling, benign-appearing papules (pityriasis lichenoides chronica or PLC).^1,2 Although historically, the term Mucha-Habermann disease has referred only to PLEVA, the term applies broadly to the entire spectrum of disease including PLC. A rare febrile ulceronecrotic variant has been reported, which is a severe form of PLEVA with high fever and marked constitutional symptoms. Lesions may self-involute and resolve completely over weeks, or new lesions occasionally may appear in crops, waxing and waning spontaneously for months to years thereafter.

Pathophysiology

Mucha-Habermann disease is not a vasculitic process despite reports of immunoglobulin and complement deposition in vessels. Fibrin is not present in the walls of vessels, and thrombi are not found in the lumen. A cell-mediated mechanism has been proposed based on a T-lymphocytic infiltrate with a cytotoxic/suppressor phenotype, diminished epidermal Langerhans cells, and a reduction of the CD4/CD8 ratio. CD30 (Ki-1) cells, which are associated with large cell lymphoma, have been identified in the infiltrate of both lymphomatoid papulosis and Mucha-Habermann disease, leading some authors to view this as a self-limited self-healing lymphoproliferative disease.^3,4  One study suggests that pityriasis lichenoides is a form of a T-cell dyscrasia, based on the presence of intraepithelial atypical lymphocytes, phenotypic abnormalities, and TCR-gamma rearrangements.⁵

Frequency

United States

The incidence of Mucha-Habermann disease in the United States has not been reported.

International

In approximately 44,000 patients seen over 10 years in 3 catchment areas in Great Britain, 17 cases of PLEVA were diagnosed.

Mortality/Morbidity

A case series of 22 children revealed a mean duration in PLEVA of 1.6 months to complete resolution and a mean duration in PLC of 7.5 months. The natural tendency of the disease is to remit spontaneously, but some cases may wax and wane over years. Disease duration may be longer in adults. A rare severe variant of PLEVA presents with a sudden eruption of diffuse coalescent necrotic ulcerations associated with high fever.⁶ Patients may develop complications such as interstitial pneumonitis, abdominal pain, malabsorption, central nervous system involvement, bacteremia, sepsis, and rheumatic manifestations. T-cell receptor clonal rearrangements of lymphocytic infiltrates have been detected in patients with PLEVA. Occasional cases (<2%) have been reported to evolve into cutaneous lymphoma, although some reports may have represented misdiagnosis of lymphomatoid papulosis.⁷

Race

All races are affected. A racial predisposition has not been reported.

Sex

A male predominance has been reported in the pediatric population and in patients presenting with febrile ulceronecrotic Mucha-Habermann disease.

Age

Most patients present during the first 3 decades of life. Studies of children have shown a variable age of onset from 3-15 years, with a mean age of 9.3 years.

Clinical

History

The history is dependent on where an individual patient's manifestations fall on the spectrum of Mucha-Habermann disease. Note the following:

• Pityriasis lichenoides et varioliformis acuta: The common variant of PLEVA presents with the abrupt appearance of multiple papules on the trunk, buttocks, and proximal extremities. Papules rapidly progress to vesicles and hemorrhagic crusts. Minor constitutional symptoms may be present. A patient with febrile ulceronecrotic PLEVA presents with acute constitutional symptoms such as high fever, malaise, and myalgias. Lesions of PLEVA may be associated with burning and pruritus.
• Pityriasis lichenoides chronica: At the subacute end of the spectrum, PLC may develop over days. PLC also is distributed over the trunk, buttocks, and proximal extremities.

Physical

The clinical presentation of Mucha-Habermann disease spans a continuum that is a function of the acuity of onset. PLEVA and PLC are not distinct diseases, but rather, they are different manifestations of the same process, although the process is accelerated in PLEVA. Note the following:

• PLEVA presents acutely with 10-50 erythematous–to–reddish brown or purpuric round or ovoid lichenoid papules that are 5-15 mm in diameter. Many papules demonstrate a pseudovesicular summit evolving to a central necrosis and a hemorrhagic crust. Note the images below.
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  Typical hemorrhagic crusted papules of pityriasis lichenoides et varioliformis acuta.

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  Close-up view of typical lesions of pityriasis lichenoides et varioliformis acuta.

• PLC presents as small erythematous–to–reddish brown papules, although with increased numbers compared to PLEVA. A fine scale usually is found, although not initially, which has been likened to frosted glass. The eruption often is polymorphic, with lesions at different stages of evolution. Note the images below.
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  Scaling papules of pityriasis lichenoides chronica.

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  Close-up view of typical pityriasis lichenoides chronica lesions. Note papules in different stages of evolution and the scale with frosted-glass appearance in the lower right-hand corner.

• Lesions that are clinically consistent with both PLEVA and PLC often are found on physical examination, and the polymorphic appearance helps distinguish Mucha-Habermann from guttate psoriasis and lichen planus.
• PLEVA lesions may evolve into lesions of PLC.
• Most lesions heal with postinflammatory changes, such as a transient or persistent leukoderma or hyperpigmentation.
• Ulceronecrotic PLEVA presents with a sudden eruption of diffuse coalescent necrotic ulcerations associated with high fever. Some lesions may resemble those of PLC, but many are large, ulceronecrotic, and covered by a black oyster shell-like crust. Necrotic ulcerating lesions may eventuate into varioliform scars.
• Dark-skinned people rarely may present with widespread macular hypopigmentation rather than the typical papular morphology.⁸ This variant is most common in children. The diagnosis depends on careful inspection, which reveals subtle PLC lesions that are compatible histologically with this diagnosis.
• In both PLEVA and PLC, lesions are scattered but discrete.
• Lesions may be distributed symmetrically or asymmetrically on the trunk, buttocks, and proximal extremities, with occasional acral involvement. Lesions may appear on the palms, soles, face, and scalp. Asymmetric or segmental nondermatomal presentations have been reported.
• Erosions and hemorrhagic crusts may be found.
• Mucosal lesions consisting of irregular erythema and superficial ulcerations on the buccal mucosa and palate have been reported.

Causes

A number of acute exanthems (eg, Mucha-Habermann disease, pityriasis rosea, acute lichen planus, guttate psoriasis, erythema multiforme) are believed to be caused by a hypersensitivity reaction to infectious agents. Familial outbreaks, clustering of cases, and comorbid symptoms have been used to support these relationships in Mucha-Habermann disease, although clear causality is lacking. Elevations of pathogen-specific antibody titers also have been offered as proof of causality, but such immunologic responses may represent epiphenomena caused by nonspecific immune responses to unknown pathogens. The most commonly reported associated pathogens are Epstein-Barr virus (EBV), Toxoplasma gondii, and human immunodeficiency virus (HIV).

Two studies implicate EBV as an etiologic factor in Mucha-Habermann disease. The cases indicate that EBV may be a trigger in PLEVA, but neither study necessarily illustrates well-characterized comorbid EBV-mediated disease. Note the following:

• In 1977, Boss et al reported a cluster of 10 cases seen over 1 year, in which eruptions were clinically consistent with PLEVA.⁹ Of these, 4 demonstrated elevated immunoglobulin G (IgG) complement-fixing antibodies to EBV. During resolution of the eruption, 3 of 4 patients demonstrated 4-fold or greater decrements in antibody titers.

• In 1989, Edwards et al described a child with a 3-week history of migratory arthralgias, monoarticular arthritis, acute pharyngitis, otitis media, and fevers to 104ºF.¹⁰ The girl developed a vesicular eruption localized primarily to the extremities, which clinically and histopathologically was consistent with Mucha-Habermann disease, with the exception of necrotic fibrin thrombi in the superficial and mid dermis. A Monospot test result was positive, and acute and convalescent serologies were consistent with a reactivation of EBV. Liver function tests were within normal limits. The patient's condition improved with treatment using oral tetracycline.

Elevated Toxoplasma gondii titers have been demonstrated in some patients with Mucha-Habermann disease. Despite an absence of clinical infection in case reports and series, more than 80% of primary Toxoplasmainfections are asymptomatic, and toxoplasmosis cannot necessarily be dismissed as a causative agent. Note the following:

• In 1969, Andreev et al were the first to suggest a link between toxoplasmosis and a recurrent PLEVA-like skin eruption in a patient with positive Toxoplasma serologies.¹¹ Cutaneous lesions reportedly responded favorably to pyrimethamine.
• In 1972, Zlatkov and Andreev reported 11 patients with PLC and found that test results were positive for toxoplasmosis in 6 patients (55%) using complement-fixations test, intradermal test with toxoplasmin, and Sabin-Feldman dye test.¹² Patients in whom test results were seropositive responded favorably to pyrimethamine, while no improvement was noted in the cutaneous lesions of 3 patients in whom results were seronegative.
• In 1987, Rongioletti et al described a patient who presented with acute onset of cutaneous lesions and histopathologic findings consistent with PLEVA.¹³ Serologic examination demonstrated enzyme-linked immunosorbent assay positivity for IgG and immunoglobulin M (IgM) and weak positive indirect fluorescence test results for IgM (1:16). Giemsa stain on the biopsy specimen failed to demonstrate Toxoplasma cysts. Spiramycin treatment was initiated, and lesions subsided over a few weeks. Convalescent serologies failed to demonstrate IgM 2 months later, although the authors still concluded that Toxoplasma species may have caused the cutaneous eruption.
• In 1997, Nassef and Hammam reported 22 patients diagnosed clinically and histopathologically with PLC and 20 healthy control subjects.¹⁴ Clinical examination for signs of toxoplasmosis only revealed axillary lymphadenopathy in 2 patients. Eight patients with PLC (36%) had a positive serodiagnosis by indirect hemagglutination versus 10% in the control group, and this difference was statistically significant. Using indirect immunofluorescence antibody tests, the difference was 36% versus 15%, respectively, but the difference was not statistically significant. All 22 patients with PLC were treated with pyrimethamine and trisulfapyrimidine, and lesions in 5 of 8 patients with seropositive results cleared completely within 2 months. None of the patients with seronegative results responded to treatment.

The first association between Mucha-Habermann disease and HIV infection was reported in 1991 by Ostlere et al.¹⁵ A patient with asymptomatic disease and a CD4⁺ T-cell count of 208 cells per microliter, diagnosed 6 months previously, presented with lesions consistent clinically and histopathologically with PLEVA. Note the following:

• In 1997, Smith et al reported a series of 5 patients with HIV infection in the early stage of disease, with CD4⁺ T-cell counts exceeding 200 cells per microliter and/or absolute lymphocyte counts within normal limits.¹⁶ The authors suggested that PLEVA serves as a marker of early–to–mid stage HIV disease.

• In 1998, Griffiths reported a patient who presented with a severely pruritic, erythematous, papular eruption that worsened as the CD4⁺ T-cell count fell from 200 to 20 cells/μ L.¹⁷ Biopsy confirmed PLC, and the disease progressed to febrile ulceronecrotic PLEVA. Dramatic improvement was attained using cyclosporine, and mild PLC-like lesions remained on maintenance doses. On saquinavir and lamivudine, the viral load became undetectable with a concomitant rise in the CD4⁺ count and a complete resolution of skin lesions. That the inherent immunologic dysregulation of HIV may play a role in Mucha-Habermann disease has been suggested.

In addition to EBV, Toxoplasma gondii, and HIV, a number of other infectious agents have been implicated. The following observations are provocative but may be chance associations. Note the following:

• Case reports have suggested that parvovirus B19 and adenovirus can trigger Mucha-Habermann disease.
• Herpes simplex has been associated with onset of the disease.
• One case report also describes resolution of PLC after tonsillectomy, with throat cultures yieldingStaphylococcus aureus and group A beta hemolytic streptococci.
• Piamphongsant similarly found coagulase-positive staphylococci on throat cultures in 4 of 10 patients, with some improvement of cutaneous lesions using oral tetracycline.¹⁸
• Freeze-dried live attenuated measles vaccine administered by injection has been associated with Mucha-Habermann disease.

Most cases of PLEVA cannot be attributed to any one cause and are idiopathic.