Pityriasis lichenoides

Pityriasis lichenoides is the name given to an uncommon rash of unknown cause. The
condition can range from a relatively mild chronic form to a more severe acute eruption.
The mild chronic form, known as pityriasis lichenoides chronica (PLC), is characterised
by the gradual development of symptomless, small, scaling papules that spontaneously
flatten and regress over a period of weeks. At the other end of a continuous clinical
spectrum of pityriasis lichenoides is the acute form of the condition. This is characterised
by the abrupt eruption of small scaling papules that develop into blisters and crusted red-
brown spots. This acute form is known as pityriasis lichenoides et varioliformis acuta
(PLEVA).

Who gets pityriasis lichenoides and why?

Pityriasis lichenoides most often affects adolescents and young adults, usually appearing
before the age of 30. It appears to be slightly more common in males. It is rare in infants
and in old age.

The cause of pityriasis lichenoides is not yet known but 3 major theories exist:

• An inflammatory reaction triggered by infectious agents

• A relatively benign form of T-cell lymphoproliferative disorder
• An immune-complex-mediated hypersensitivity vasculitis

Infections that have been associated with both PLC and PLEVA include:

• Toxoplasma gondii
• Epstein-Barr virus
• HIV
• Cytomegalovirus
• Parvovirus (fifth disease)
• Staphylococcus aureus
• Group A beta-haemolytic streptococci

Lymphoproliferative disordersare conditions in which there excessive numbers of

lymphocytes (T- and B-cells), including lymphoma (a malignant growth of lymphocytes).
The idea that pityriasis lichenoides may be a lymphoproliferative disorder arises because
lesions of patients with pityriasis lichenoides showed the presence of immune T-cells
with specific CD30+ markers or antigens in PLEVA,and loss of CD7 antigens on T-cells
in PLC. These characteristics of T cells are indicators of lymphoproliferative disorders.

The third theory behind the cause of pityriasis lichenoides is the detection of circulating
immune complexes (aggregations of antigens and antibodies) deposited in the skin in
some patients with the condition.
What are the signs and symptoms of pityriasis
lichenoides?
Pityriasis lichenoides chronica (PLC)

PLC has a more low-grade clinical course than PLEVA. PLC lesions may appear over the
course of several days, weeks or months. Lesions at various stages may be present at any
one time.

• Initially a small pink papule occurs that turns a reddish-brown colour

• Usually a fine mica-like adherent scale attached to the central spot develops. This
can be peeled off to reveal a shiny, pinkish brown surface.
• Over several weeks the spot flattens out spontaneously and leaves behind a brown
mark, which fades over several months.

PLC most commonly occurs over the trunk, buttocks, arms and legs, but may also occur
on the hands, feet, face and scalp. Unlike PLEVA, lesions are not painful, itchy or
irritable. Often patients with PLC have exacerbations and relapses of the condition, which
can last for months or years.

Pityriasis lichenoides et varioliformis acuta (PLEVA)

PLEVA is characterised by red patches that quickly evolve into papules 5-15 mm in
diameter. They are often covered with a fine mica-like adherent scale. The centre of the
papules often becomes filled with pus and blood, or eroded with overlying red-brown
crust.

PLEVA most often occurs on the trunk and extremities but sometimes may also be
diffuse and widespread, covering any part of the body. Unlike PLC, which has no
apparent symptoms, patients with PLEVA experience burning and itchiness.

A subtype of PLEVA is febrile ulceronecrotic Mucha-Habermann disease. This

condition is different to PLEVA in that black or necrotic papules rapidly develop into
large coalescent crusted ulcers, blood-filled blisters, and pustules. Mucha-Habermann
lesions are usually very painful. The ulcers may become infected. In addition, systemic
systems may include high fever, sore throat, diarrhoea, abdominal pain, central nervous
system symptoms, lung disease, enlarged spleen, arthritis, sepsis, anaemia, and
conjunctival ulcers. In some cases the condition can lead to death.

What is the treatment of pityriasis lichenoides?

Pityriasis lichenoides may not always respond to treatment and relapses often occur when
treatment is discontinued. If the rash is not causing symptoms, treatment may not be
necessary. Large ulcerations found in febrile ulceronecrotic Muchas-Habermann disease
require local wound care.
In cases where treatment is necessary, there are several different therapies available.
Current recommended first-line therapies include:

• Sun exposure may help to resolve lesions but sunburn should be avoided.
• Topical steroids to reduce irritation. In more recent years concerns raised about
their side effect profile has led to the increased use of nonsteroidal topical
immunomodulators.
• Topical immunomodulators such as tacrolimus or pimecrolimus. Tacrolimus
ointment applied twice daily has been used successfully to treat patients with
PLC.
• Oral antibiotics. The most common antibiotics used are erythromycin and
tetracycline. These antibiotics have been used to treat both PLC and PLEVA.

Second-line therapies include:

Phototherapy – artificial ultraviolet radiation treatment with UVB or PUVA has been
used with varying success both in patients with PLEVA and in those with PLC.

Third-line therapies include:

• Systemic steroids
• Methotrexate given orally or by IM injection has been used in PLC and PLEVA.
It is often used to treat febrile ulceronecrotic Muchas-Habermann disease
• Acitretin
• Dapsone
• Ciclosporin
• For more resistant and severe disease a combination of the above may be used

Pityriasis lichenoides may persist for some years but is generally fairly harmless,
although there have been rare reports of malignant transformation. Because of this,
regular follow-up is recommended.
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.

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.

• 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 Toxoplasma infections 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 yielding Staphylococcus 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.

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).

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.

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.

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.

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.