Liken Simpleks Kronikus

Definisi

Nama lain dari liken simpleks kronikus adalah neurodermatitis sirkumskripta (NS). Istilah
tersebut pertama kali dipakai oleh Vidal, oleh karena itu juga disebut liken Vidal.

Peradangan kulit kronis, gatal, sirkumskrip, ditandai dengan kulit tebal dan garis kulit tampak
lebih menonjol (likenifikasi) menyerupai kulit batang kayu, akibat garukan atau gosokan yang
berulang-ulang karena berbagai rangsangan pruritogenic.

 A chronic, severely pruritic disorder characterized by one or more lichenified plaques.

 Most common sites of involvement are scalp, nape of neck, extensor aspects of
extremities, ankles, and anogenital area.
 Pathology consists of hyperkeratosis, hypergranulosis, psoriasiform epidermal
hyperplasia, and thickened papillary dermal collagen.

Asociated with intense itch and characteristic morphologic findings. Each of these disorders
may present in patients with atopic and contact dermatitis. However, these disorders often
present in the absence of atopic disease and may be associated with underlying systemic
disease.

Epidemiologi

Lichen simplex chronicus (LSC) and prurigo nodularis (PN) are phenotypes that are caused by
repeated itch- ing, scratching, and rubbing of the skin. They can be associated with multiple
etiologies of dermatologic and/or systemic disease.35 However, some use these terms (LSC
and PN) to describe a specific diagnosis, which excludes other dermatologic disorders that
present with these lesions, such as AD (ie, nodular prurigo of Hyde).36,37 The epidemiology
of LSC and PN is not well-defined, owing to scant studies and the different definitions used in
the studies. Little is known about the descriptive epidemiology of PN. A retrospective
population-based study in Taiwan found the incidence of LSC to be 25 to 28 versus 17.8 per
10,000 person-years in those with versus those with- out a history of anxiety disorders.38 A
cross-sectional study found that LSC and PN were encountered in 3% and 2.1% of dermatology
visits, respectively.9 PN more commonly occurs in adults, but can occasionally affect
children.9,39,40 Patients with PN in the setting of AD have been found to have an earlier age
of onset as compared to those without AD.41 LSC may be more common in patients of Asian
descent for reasons unknown.42

Etiologi dan Patogenesis

Pruritus memainkan peran sentral dalam timbulnya pola reaksi kulit berupa likenifikasi dan
prurigo nodularis. Hipotesis mengenai pruritus dapat oleh keh karena adanya penyakit yang
mendasari, misalnya gagal ginjal kronis, obstruksi saluran empedu, limfoma Hodgkin,
hipertiroidia, penyakit kulit seperti dermatitis atopik, dermatitis kontak alergik, gigitan
serangga, dan aspek psikologik dengan tekanan emosi.

Pada prurigo nodularis jumlah eosinophil meningkat. Eosinofil berisi protein X dan protein
kationik yang dapat menimbulkan degranulasi sel mas. Jumlah sel Langerhans juga bertambah
banyak. Saraf yang berisi CGRP (calcitonin gene-related peptide) dan SP (substance P), bahan
imunoreaktif, jumlahnya di dermis bertambah pada prurigo nodularis, tetapi tidak pada
neurodermatitis sirkumskripta. SP dan CGRP melepaskan histamin dari sel mas yang
selanjutnya akan memicu pruritus. Ekspresi faktor pertumbuhan saraf p75 pada membran sel
Schwan dan sel perineurum meningkat, mungkin ini menghasilkan hiperplasi neural.

LSC is induced by rubbing and scratching, whereas prurigo nodules are induced by picking
and scratch- ing secondary to itch. Some authors suggest that PN is a form of LSC.43,44 These
two disorders may represent a spectrum of manifestations secondary to chronic itch.

Various factors incite itch in both disorders and not all are well understood. Both types of
lesions are com- monly found in patients with AD along with xerosis and other signs and
symptoms of AD. Some stud- ies found that patients with LSC and PN have high rates of atopic
disease and/or a history of AD.39,41,45,46 “Besnier prurigo” refers to the prurigo nodules seen
in AD. Prurigo nodules may also occur in other der- matoses, such as contact dermatitis47 and
pemphigoid nodularis, a rare variant of bullous pemphigoid.48,49 LSC may develop
superimposed on other dermato- ses, including contact dermatitis,50-52 psoriasis, Candida,
and tinea infections.53

There may be underlying systemic causes of pruritus in patients with PN and LSC without AD.
These causes include renal insufficiency, hyper- or hypothyroidism, liver failure, hepatitides B
and C viruses even without liver failure, HIV disease, Helicobacter, mycobacterial or parasitic
infection, or an underlying hematologic or solid-organ malignancy, including Hodgkin disease,
and gastric and bladder cancers.54-59 PN also has been reported to occur in the setting of celiac
disease and/or dermatitis herpetiformis.
LSC, neuropathy, and radiculopathy has been sug- gested in a subset of patients.35,62

PN and LSC appear to have a bidirectional relation- ship with emotional and psychological
factors. A ret- rospective population-based study in Taiwan found that persons with anxiety
disorders had significantly higher risk of subsequently developing LSC.38 On the other hand,
patients with LSC and PN have higher rates of depression, anxiety, obsessive-compulsive
disorder, and other psychological disorders.39,63-67 One study found that 72% of patients
thought that psycho- social problems were of relevance.39 The higher rates of psychological
disorders may be partly a result of the detrimental effects of the chronic itchiness and sequelae
of their skin disease.

Several pathways have been postulated for height- ened perception to touch and itch in patients
with LSC and PN. These include cellular and neurochemi- cal changes at the level of cutaneous
nerves in lesions, the spinal cord, and the central nervous system. PN lesions were found to
have increased cutaneous nerve fibers (neural hyperplasia) and increased staining for the
neuropeptides calcitonin gene-related peptide (CGRP) and substance P, but not tyrosine
hydroxylase, vasoactive intestinal polypeptide, and the C-flanking region of neuropeptide Y.68
Nerve growth factor is overexpressed in PN lesions and is implicated in the pathogenesis of
cutaneous neural hyperplasia and upregulated expression of neuropeptides, such as CGRP and
substance P.69 CGRP and substance P may be modulators of itch and upregulate secretion of
pro- inflammatory cytokines, including tumor necrosis fac- tor alpha, interleukin (IL)-1 and
IL-8 within lesional skin of PN.68 Keratinocytes also express transient receptor potential cation
channel subfamily V member 1 (TRPV1) channels, which play important roles in sensation of
itch, heat and pain. TRPV1 receptors are greatly upreg- ulated in PN.70 IL-31 is produced by
T cells and may be a direct inflammatory mediator of itch.71 One study found that IL-31 levels
were dramatically increased in PN lesions of atopic skin disease.72 Neurotransmitters that
affect mood, such as dopamine, serotonin, or opioid peptides, modulate perception of itch via
descending spinal pathways.73 Finally, environmental factors, such as heat, sweat, and
irritation have been implicated in inducing itch in anogenital LSC.53

Diagnosis

Anamnesis

Penderita mengeluh gatal sekali, bila timbul malam hari dapat mengganggu tidur. Rasa gatal
memang tidak terus menerus, biasanya pada waktu tidak sibuk, bila muncul sulit ditahan untuk
tidak digaruk. Penderita merasa enak bila digaruk; setelah luka, baru hilang rasa gatalnya untuk
sementara (karena diganti dengan rasa nyeri).

Lesi biasanya tunggal, pada awalnya berupa plak eritematosa, sedikit edematosa, lambat laun
edema dan eritema menghilang, bagian tengah berskuama dan menebal, likenifikasi dan
ekskoriasi; sekitarnya hiperpigmentasi, batas dengan kulit normal tidak jelas. Gambaran klinis
dipengaruhi juga oleh lokasi dan lamanya lesi.

NS, tidak biasa terjadi pada anak, tetapi pada usia dewasa-manula; pundak insiden pada usia
antara 30 hingga 50 tahun. Perempuan lebih sering menderita daripada laki-laki. Letak lesi
dapat timbul di mana saja, tetapi yang biasa ditemukan ialah di scalp, tengkuk, samping leher,
lengan bagian ekstensor, pubis, vulva, skrotum, perianal, medial tungkai atas, lutut, lateral
tungkai bawah, pergelangan kaki bagian depan, dan punggung kaki. Neurodermatitis di daerah
tengkuk (lichen nuchae) umumnya hanya pada perempuan, berupa plak kecil di tengah tengkuk
atau dapat meluas hingga ke scalp. Biasanya skuama menyerupai psoriasis.

Variasi klinis NS dapat berupa prurigo nodularis, akibat garukan atau korekan tangan penderita
yang berulang-ulang pada suatu tempat. Lesi berupa nodus berbentuk kubah, perbukaan
mengalami erosi tertutup krusta dan skuama, lambat laun menjadi keras dan berwarna lebih
gelap (hiperpigmentasi). Lesi biasanya multiple, lokalisasi tersering di ekstremitas, berukuran
mulai beberapa milimeter sampai 2 cm.
Severe itching is the hallmark of LSC and PN. Itching may be paroxysmal, continuous, or
sporadic, local- ized or diffuse. Itching may be described by patients as burning, stinging, or a
creepy-crawly sensation akin to formication. Patients may not be aware of itching and
scratching that occurs during sleep time. Patients may also develop habitual scratching or
picking of lesions, even when they are not itchy. Itch is often triggered by sweating, heat,
friction, extreme humidity or dry- ness, irritation from personal care products or clothing,
and/or times of psychological distress.53,54 LSC and PN are associated with moderate to
severe quality-of-life impairment74-77 and sexual dysfunction.78

Pemeriksaan Fisik

In LSC, repeated rubbing and scratching gives rise to lichenified, dry, and scaly plaques with
or without excoriations. Hyperpigmentation and hypopigmenta- tion can be seen, particularly
in patients with skin of color. The most common sites of involvement are the scalp, the nape
of the neck, the ankles, the extensor aspects of the extremities, and the anogenital and vul- var
regions.79 The labia majora in women and the scro- tum in men (Fig. 23-5) are the most
common sites of genital involvement.45 The upper inner thighs, groin, nipple, and areola also
may be affected.79

Prurigo nodules are firm to hard on palpation, varying in size from 0.5 cm to >3.0 cm, and
numbering from few to hundreds. The surface may be hyperkeratotic or crateriform. There is
often overlying excoriation. Pruri- tus is usually severe. Limbs are affected in most cases,
especially the extensor aspects (Fig. 23-6). The abdo- men and sacrum were the next most
common sites of involvement in one study.39 Face and palms are rarely involved. Nodules
may occur on any site that can be reached by the patient. There can be a characteristic “butterfly
sign” with lesional sparing on the upper back. However, some patients may even develop nod-
ules on hard-to-reach areas secondary to using back- scratchers, knives, forks, brushes, or other
instruments to scratch. Nodules may persist for months to years and resolve with
postinflammatory hyperpigmenta- tion or hypopigmentation and scarring.

In patients with AD, the intervening skin is often lichenified and xerotic, and patients may have
other signs of atopy, such as Dennie-Morgan fold or palmar hyperlinearity. In nonatopic
patients, cutaneous signs of underlying systemic disease or lymphadenopathy, signifying
lymphoma, may be present.

Pemeriksaan Laboratorium

In patients with LSC or PN in whom an underlying systemic cause of pruritus is suspected, a

complete blood count with differential and renal, liver, and thyroid function tests may be
ordered. Testing for HIV, diabetes (fasting glucose and/or hemoglobin A1C) may be
indicated.35 A chest radiograph may be obtained to screen for lymphoma. The need for a more
extensive evaluation should be individualized based on patient history and results of the
aforemen- tioned tests.

Additional testing for iron deficiency, erythrocyte sedimentation rate, gliadin antibody, zinc,
cobalamin, total porphyrins, and stool examination for Strongyloides stercoralis may also be
indicated. Ultrasound of the abdomen or lymph nodes may be indicated to rule out liver or
kidney disease or lymphoma. Breath test for Helicobacter, lactose, and sorbitol intolerance
may be indicated. Magnetic resonance imaging of the cervical spinal column is called for if the
patient has localized LSC or PN (eg, brachioradial distribution).

Pemeriksaan Khusus

Gambaran histopatologik neurodermatitis sirkumskripta berbentuk ortokeratosis,

hipergranulosis, akantosis dengan rete ridges memanjang teratur. Bersebukan sel radang
limfosit dan histiosit di sekitar pembuluh darah dermis bagian atas, fibroblast bertambah,
kolagen menebal. Pada prurigo nodularis akantosis pada bagian tengah lebih tebal, menonjol
lebih tinggi dari permukaan, sel Schwan berproliferasi, dan terlihat hiperplaso neural. Kadang
terlihat krusta yang menutup sebagian epidermis.

On histopathologic sections, LSC shows varying degrees of hyperkeratosis with parakeratosis

and ortho- keratosis, hypergranulosis, and psoriasiform epidermal hyperplasia. The papillary
dermis shows thickening of collagen with coarse collagen bundles and verti- cal streaks. There
is a variable inflammatory infiltrate around the superficial vascular plexus with lympho- cytes,
histiocytes, and eosinophils. A biopsy may also reveal a primary pruritic disorder, such as
psoriasis, that has led to secondary lichenification. Direct immu- nofluorescence may be
needed to rule out autoimmune skin disease, such as bullous pemphigoid or dermati- tis
herpetiformis. Polymerase chain reaction testing for mycobacteria may be needed if
histological investiga- tion finds granulomatous inflammatory infiltrate.

The epidermal findings in PN are similar to LSC. The lesion is more papular with bulbous
epidermal hyperpla- sia. Papillary dermal changes also resemble LSC. There may be cutaneous
neural hypertrophy with thickened nerve bundles and an increase in nerve fibers by S-100
staining. This finding may not be seen in all cases.80

Diagnosis Banding

Diagnosis neurodermatitis sirkumskripta didasarkan gambaran klinis, biasanya tidak terlalu

sulit. Namun perlu dipikirkan kemungkinan penyakit kulit lain yang memberikan gejala
pruritus, misalnya liken planus, liken amyloidosis, psoriasis, dan dermatitis atopik.

Most likely

 Lichenified atopic eczema

 Lichenified psoriasis
 Hypertrophic lichen planus

Consider

 Genital : extramammary Paget disease

Always rule out

 Vulva, perianally: underlying lichen sclerosus, human papillomavirus, or tinea cruris

 Scrotum: underlying human papillomavirus or tinea cruris

Komplikasi

Sleep studies show that disturbances in the sleep cycle in LSC are present. Non-rapid eye
movement sleep is disturbed and patients have an increased arousal index (brief awakenings
from sleep) caused by scratching.81

Patients with LSC and PN have higher rates of depression, anxiety, obsessive-compulsive
disorder, and other psychological disorders.39,63-67
A retrospective population-based cohort study found that patients with LSC had higher baseline
rates of diabetes, hypertension, hyperlipidemia, cardiovas- cular disease, peripheral arterial
disease, chronic kid- ney disease, depression, and anxiety, and an increased risk of developing
erectile dysfunction.78

Prognosis

Prognosis bergantung pada penyebab pruritus (penyakit yang mendasari), dan status psikologik
penderita.

Both diseases run a chronic course with persistence or recurrence of lesions. The mean duration
of PN was found to be 77.5 months,35 whereas that of anogeni- tal LSC was found to be 30.6
months.82 LSC and PN in association with systemic disease may have a more prolonged course
than other etiologies.35 The pres- ence of PN in patients with renal pruritus is associated with
more prolonged itch.83 Exacerbations can occur in response to emotional stress and exogenous
stimuli.

Tatalaksana

Secara umum perlu dijelaskan kepada penderita bahwa garukan akan memperburuk keadaan
penyakitnya, oleh karena itu harus dihindari. Untuk mengurangi rasa gatal dapat diberikan
antipruritus, kortikosteroid topical atau intralesi, produk ter.

Antipruritus dapat berupa antihistamin yang mempunyai efek sedative (contoh: hidroksizin,
difenhidramin, prometazin) atau transquilizer. Dapat pula diberikan secara topical krim
doxepin 5% dalam jangka pendek (maksimum 8 hari). Kortikosteroid yang dipakai biasanya
berpotensi kuat, bila perlu ditutup dengan penutup impermeable; kalua masih tidak berhasil
dapat diberikan secara suntikan intralesi. Salep kortikosteroid dapat pula dikombinasi yang
mempunyai efek antiinflamasi. Ada pula yang mengobati dengan UVB dan PUVA. Perlu dicari
kemungkinan ada penyakit yang mendasari, bila memang ada harus juga diobati.
Figure 23-7 Stepwise management of prurigo nodularis and lichen simplex chronicus. BB, broadband; NB,
narrowband; PUVA, psoralen and ultraviolet A; UVA, ultraviolet A; UVB, ultraviolet B.

Figure 23-7 outlines the stepwise management of LSC and PN. Treatment is aimed at
interrupting the itch– scratch cycle. Both components should be addressed. Systemic causes of
itch should be identified and addressed. In both conditions, first-line measures to control itch
include potent topical corticosteroids as well as nonsteroidal antipruritic preparations such as
menthol, phenol, or pramoxine. Emollients are an important adjunct, particularly for those
patients with AD. Intralesional steroids, such as triamcinolone acetonide, given in varying
concentrations according to the thickness of the plaque or nodule are beneficial. Topical
tacrolimus has been successfully employed as a steroid-sparing agent, but may require
application under occlusion to improve transcutaneous absorption. Sedating antihistamines,
such as hydroxyzine, or tricy- clic antidepressants, such as doxepin, may be used to abolish
nighttime itch in both conditions. An open-label study of 9 patients with conventional therapy-
resistant PN found that daily montelukast and fexofenadine was effective at reducing itch in
75% of patients.84 Selective serotonin reuptake inhibitors have been recommended for relief
of daytime pruritus or in patients with comor- bid obsessive-compulsive disorder.53

Capsaicin, calcipotriene, and cryotherapy, with or without intralesional steroid injections, have
all been successfully used in PN. Both broadband and narrow- band ultraviolet B, as well as
topical or oral psoralen and ultraviolet A (PUVA) show efficacy and are indi- cated in
widespread cases. The 308-nm excimer mono- chromatic light, UVA1 phototherapy, and
naltrexone were all effective in small series.85-87 Thalidomide and lenalinomide,88 low-dose
methotrexate,89 and cyclo- sporine90 also are beneficial, albeit with some adverse effects
reported.

The importance of avoiding scratching should be addressed with the patient. Nails should be
kept short and mittens can be used to prevent scratching. Occlu- sive measures, such as plastic
films, topical steroid impregnated tape, or Unna boots may be needed in widespread or
refractory cases