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MINISTRY OF HEALTH
UZBEKISTAN
TASHKENT MEDICAL ACADEMY
medical Faculty
Medical-Pedagogical faculty
Medical-Prophylactic faculty
Department of Skin and Venereal Diseases
Lecture 4
Lichenoid dermatosis: psoriasis, lichen ruber planus. Neurodermatosis. Allergodermatosis.
Dermatitis. Toxicodermia. Professional dermatosis’. Eczema. Modern methods of treatment.
The drafters: doc. Musaeva N.Sh.
Ass. Karimova M.K.
Tashkent 2016
Plan and organizational structure of the lecture:
1.Introduction words defined initial level of knowledge, the explanation of problems lectures
2. Lichenoid dermatosis: psoriasis, lichen ruber planus. Neurodermatosis.
3.Allergodermatosis. Dermatitis. Toxicodermia. Professional dermatosis’. Eczema.
4.Modern methods of treatment.
SUBJECT: LECTURE № 4
Lichenoid dermatosis: psoriasis, lichen ruber planus. Neurodermatosis. Allergodermatosis.
Dermatitis. Toxicodermia. Professional dermatosis’. Eczema. Modern methods of treatment.
Psoriasis is a multifactorial hereditary, chronic recurrence dermatosis. Characterized by rash on
the skin liberally, plentifully shelled papules with a tendency to spread and Enhancement of the
skin over the life of the patient. In some cases, cause serious changes in various organs and
tissues (joints, spine, liver, kidneys). There are various theories the appearance of psoriasis.
Phase currents psoriasis: - progressive - stationary - retrogressive. Types of psoriasis based on
the seasonality of relapses: - winter, summer, indefinitely. In psoriasis, there are certain areas of
localization. Pathomorphologic changes characteristic of psoriasis: parakeratosis, acanthosis,
papillomatosis, agranulez formation microabsessus Munro in the epidermis.
Genetic Factors
Depending upon the series, a positive family history has been reported
by 35% to 90% of patients with psoriasis. Based on a large survey-based
study in Germany, if both parents had psoriasis, the risk of their child
developing psoriasis was 41%, whereas if only one parent were affected,
the risk was 14%; the risk was 6% if just one sibling had psoriasis12.
Analysis of concordance rates among monozygotic and dizygotic
twins is another method for examining the influence of genetic factors
on a disease. Farber and Nall13 reviewed the published data from twin
pair studies in psoriasis. Of 141 monozygotic twin pairs, 82 were concordant
for psoriasis and 59 were discordant; of 155 dizygotic twin
pairs, only 31 were concordant and 124 were discordant for psoriasis.
Thus, there is a two- to threefold increased risk of psoriasis in monozygotic
twins as compared to dizygotic twins7, implying that genetic
factors are important. The distribution of the lesions, the severity, and
the age of onset were similar in the monozygotic twin pairs, whereas
these features differed in the dizygotic twin pairs. This observation
suggested that genetic factors also play a role in the clinical course of
psoriasis.
HLA studies
Histocompatibility antigens (HLA) are surface antigens on human
cells, and the corresponding chromosomal region is called the major
histocompatibility complex (MHC). It is situated on the short arm (p)
of chromosome 6. Psoriasis is associated with HLA-Cw6, with the Genetic Factors
Depending upon the series, a positive family history has been reported
by 35% to 90% of patients with psoriasis. Based on a large survey-based
study in Germany, if both parents had psoriasis, the risk of their child
developing psoriasis was 41%, whereas if only one parent were affected,
the risk was 14%; the risk was 6% if just one sibling had psoriasis12.
Analysis of concordance rates among monozygotic and dizygotic
twins is another method for examining the influence of genetic factors
on a disease. Farber and Nall13 reviewed the published data from twin
pair studies in psoriasis. Of 141 monozygotic twin pairs, 82 were concordant
for psoriasis and 59 were discordant; of 155 dizygotic twin
pairs, only 31 were concordant and 124 were discordant for psoriasis.
Thus, there is a two- to threefold increased risk of psoriasis in monozygotic
twins as compared to dizygotic twins7, implying that genetic
factors are important. The distribution of the lesions, the severity, and
the age of onset were similar in the monozygotic twin pairs, whereas
these features differed in the dizygotic twin pairs. This observation
suggested that genetic factors also play a role in the clinical course of
psoriasis.
HLA studies
Histocompatibility antigens (HLA) are surface antigens on human
cells, and the corresponding chromosomal region is called the major
histocompatibility complex (MHC). It is situated on the short arm (p)
of chromosome 6. Psoriasis is associated with HLA-Cw6, with the Several conclusions regarding
the genetic factors in psoriasis can be
drawn from recent GWAS18,19. First, most of the genes that have been
implicated have immune-related functions, underscoring the importance
of the innate and adaptive immune systems in the pathogenesis
of psoriasis; in contrast, relatively few genes that encode skin-specific
proteins have been associated with psoriasis. Second, thus far surprisingly
few interactions among the genetic variants have been identified
(with the exception of HLA-Cw6 and ERAP-1; see below). Third, associated
genes encode proteins with roles in particular immunologic and
signaling pathways, especially those involving tumor necrosis factor
(TNF), NF-κB, interferons (IFN) and interleukin (IL)-23/Th17 cells
(see Immunopathogenesis)19,20. Lastly, the ERAP1 gene encoding an
aminopeptidase involved in MHC class I antigen processing is only
associated with psoriasis risk in individuals carrying the HLA-Cw6
risk allele, providing evidence for the role of an MHC-restricted
antigen and its presentation through HLA-C in the pathogenesis of
psoriasis.
Functional genomic studies
Microarray technology has been utilized to obtain a comprehensive
picture of the genes expressed in psoriatic skin21. More than 1300 genes
were found to be differentially expressed when compared to normal
human skin. This group of genes included known markers of psoriasis
in the skin, but it also contained numerous genes not known to be
expressed in the skin. These analyses confirmed the known involvement,
on a genomic scale, of T cells and dendritic cells (DCs), providing
evidence for sustained chronic T-cell activation and persistence in
psoriatic epidermis.
Microarray-based comparison between the transcriptome of lesional
skin from patients with psoriasis versus atopic dermatitis have
revealed not only differences in expression of genes with immune
function, but also differences in genes expressed by keratinocytes. For
example, skin-derived antimicrobial proteins were expressed at high
levels in psoriatic skin but at low levels in skin affected by atopic
dermatitis22.
PATHOGENESIS
Because it primarily affects the interfollicular epidermis, psoriasis was
long regarded as an epidermal disease in which the biochemical or cellular
defect resided within the keratinocyte. Accordingly, prior to the
early 1980s23, a number of biochemical mediators, enzymes and pathways
involved in epidermal function were incriminated as being abnormal
in psoriasis, including cyclic AMP, eicosanoids, protein kinase C,
phospholipase C, polyamines and transforming growth factor (TGF)-α.
Although associated immunologic abnormalities were reported in the
late 1970s24, a major paradigm shift occurred when T-cell suppressive
agents such as cyclosporine were found to result in significant improvement
of psoriasis25. For the past two decades, psoriasis has been regarded
as a T-cell-driven disease25. The role of lymphocyte subsets as well as
cytokines involved in chemotaxis, homing and activation of inflammatory
cells has been extensively investigated, culminating in the development
of novel therapeutic approaches25. Although some regard psoriasis
as an autoimmune disease, to date no true autoantigen has been definitively
identified.
Immunopathogenesis
Role of T cells and dendritic cells
The association of psoriasis with particular MHC alleles, such
as HLA-Cw6, and (in individuals carrying such alleles) variants in
the ERAP1 gene encoding an aminopeptidase involved in antigen
processing strongly suggests a pathogenetic role for antigenpresenting
cells and T cells (Fig. 8.1). The presence of specific T-cell
subsets within the epidermis and dermis of lesional skin is well documented
(see below). In addition, a number of compounds that affect
T-cell function (e.g. by targeting the IL-2 receptor, CD2, CD11a and
CD4) were found to result in clinical improvement of psoriasis25.
Another argument supporting involvement of the adaptive immune
system is the disappearance or development of psoriasis following
hematopoietic stem cell transplantation26,27. In addition, analysis of
lesional T cells has shown oligoclonality, indicating potential antigenspecific
expansion of T-cell subpopulations, possibly triggered by
exogenous microbial or viral antigens or cross-reacting autoantigens,
e.g. keratins28.
Animal models for psoriasis have also demonstrated the importance
of T cells. In xenograft models in which uninvolved psoriatic skin was
transplanted onto immunodeficient mice, donor immune cells (in particular
resident T cells) were capable of expanding and inducing the
complete lesional phenotype29. Induction of psoriatic lesions in these
models was also shown to be dependent on TNF-α and on IFN-α
derived from plasmacytoid DCs (pDCs)29,30. These experiments demonstrated
that T cells can trigger psoriasis in a suitable patient-derived
environment.
In humans, several cell types have been implicated in the initiation
and maintenance of psoriatic lesions. Most of the epidermal T cells are
CD8+, whereas the dermal infiltrate is a mixture of CD4+ and CD8+
cells. The majority of the cells in both locations are memory T cells
that express cutaneous lymphocyte antigen (CLA; the skin homing
receptor) and chemokine receptors such as CCR4. Expression of α1β1
integrin (VLA-1) on psoriatic T cells, which allows their interaction
with basement membrane collagen IV, is key for the entrance of these
cells into psoriatic epidermis and establishment of the psoriatic epithelial
phenotype (see Fig. 8.1)31. Natural killer (NK) T cells represent
another subset of T cells that are part of the innate immune system
and are found in psoriatic skin lesions; they interact with CD1d on
keratinocytes. The resulting production of IFN-γ could contribute to
additional immune stimulation32.
DCs are present in both uninvolved and lesional psoriatic skin, and
because of their potent immunostimulatory capacity, they are likely to
be involved in its pathogenesis. There is an increased number of dermal
DCs in psoriatic skin, and they have an enhanced ability to activate T
cells when compared to DCs from normal skin33. DC phenotype and
function are quite plastic, with the ability to differentiate into potent
proinflammatory DCs that produce inducible nitric oxide synthase
(iNOS) and TNF-α (referred to as TIP [TNF/iNOS-producing] DCs)34.
The role of DCs in psoriasis has been validated by the presence of a
prominent genomic DC signature and the decrease of DCs during effective
targeted therapy35.
Based upon studies in humans and a xenograft model, another type
of DC, the pDC, was shown to initiate psoriasis via the production of
IFN-α30. Complexes of self DNA or RNA (from keratinocytes) plus
antimicrobial peptide LL37 trigger IFN-α release by pDCs via a Toll-like
receptor 9 (TLR9)-dependent mechanism (see Fig. 8.1). This leads to a
breaking of tolerance to self nucleic acids and potentially explains the
start of the inflammatory cascade in psoriasis36,37.
The presence of neutrophils in the epidermis, either in spongiform
pustules of Kogoj or in microabscesses of Munro, is a typical histopathologic
feature of psoriasis, especially acute or pustular forms. Neutrophils
are typically prominent in active lesions and in the marginal
zone of expanding plaques, but, in contrast to T cells, they are not a
consistent feature of lesional skin. Although activated neutrophils
could contribute to its pathogenesis, they are not considered to be the
primary cause of psoriasis.
Prominent angiogenesis is observed in plaques of psoriasis. There is
increased expression of vascular endothelial growth factor (VEGF)38,
and anti-VEGF therapy leads to improvement in mouse models of
psoriatic inflammation39.
Cytokines and chemokines
Psoriasis is considered to be a disease with prominent involvement of
helper T-cell subsets and their secreted cytokines40. Increased amounts
of Th1 cytokines (IFN-γ and IL-2) are observed, whereas levels of the
anti-inflammatory cytokine IL-10 are reduced. Based on animal studies
and measurements in lesional skin, IL-12, IL-23 and IL-15 are likely
to contribute to the disease. The striking response of psoriasis to ustekinumab,
a human monoclonal antibody against the p40 subunit of IL-12
and IL-23, provides additional evidence for the role of cytokines. It is
thought that IL-23 (produced by DCs) stimulates Th17 cells to release
IL-17 and IL-22; the concerted action of these cytokines leads to proliferation
of keratinocytes and dermal inflammation (see Fig. 8.1)41. Of
note, circulating levels of IL-22 correlate with disease severity. It has
also been proposed that there is a distinct subset of IL-22-producing
helper T cells (Th22 cells) that contribute to the pathogenesis of psoriasis42,43.
The IL-17-producing T cells in psoriatic epidermis might
have a cytotoxic phenotype, qualifying them as Tc17 cells44.
IFN-γ is released by activated T cells and NK T cells in the epidermis,
and it activates members of the STAT transcription factor family, which
drive the expression of a large number of immune-related genes that
have roles in psoriasis pathogenesis. The IFN-γ-activated pathway is a
key feature of psoriasis and explains several phenotypic alterations such
as vasodilation (by the induction of iNOS) and accumulation of T cells
(via the expression of various chemokines).
The innate immune cytokines IL-1, IL-6 and TNF-α are upregulated
in psoriatic skin. TNF-α is a particularly relevant cytokine and its
importance is underscored by the therapeutic efficacy of TNF-α inhibitors
(see Treatment).
Chemokines are important mediators in the trafficking of leukocytes,
and the increased presence of several chemokines and their cognate
receptors in psoriatic lesions has been extensively documented. CXCL8
is thought to mediate the often-prominent infiltration by neutrophils.
CCL17, CCL20, CCL27 and CXCL9-11 are implicated in attracting T
cells to the psoriatic plaque. A pDC-attracting chemokine, chemerin,
is increased in psoriatic skin and might contribute to the early recruitment
of pDCs into psoriatic lesions45.
Innate immunity and role of keratinocytes
In the skin, various cell types are involved in innate (non-adaptive)
immune response pathways. These include DCs (myeloid DCs and
pDCs), NK T cells and neutrophils (see above), as well as epidermal
keratinocytes. For example, keratinocytes constitutively express antimicrobial
proteins such as β-defensin-1 (hBD1) and secretory leukocyte
protease inhibitor (SLPI), which have direct antimicrobial activity
against a broad spectrum of pathogens. In addition, keratinocytes can
be stimulated to express a wide variety of other inducible antimicrobials
such as hBD2, the cathelicidin LL37, and SKALP/elafin46. In addition
to these effector molecules, keratinocytes express TLRs and secrete
signaling molecules such as IL-1, IL-6, IL-8 and TNF-α. Interestingly,
the antimicrobial effector protein hBD2 was also shown to have chemotactic
activity via CCR6 and to bind to TLR-4. Since most of these proteins are highly expressed in
lesional psoriatic skin, it is likely that proteins are highly expressed in lesional psoriatic skin, it is
likely that they are involved in the initiation or control of the inflammatory process; however,
their precise roles remain to be determined.
Any model of the pathogenesis of psoriasis also has to account for
the dramatically increased proliferation rate of keratinocytes. The
cytokines and chemokines found in lesional skin are generally not
mitogenic for keratinocytes. For example, IFN-γ, a prominent Th1
cytokine, is itself antiproliferative, but it was found to be a crucial factor
in supernatants of lesion-derived T-cell clones that could drive keratinocyte
stem cell proliferation47.
Keratinocytes within psoriatic plaques express STAT-3, suggesting
that this transcription factor might be of pathogenetic importance. In
a transgenic animal model, epidermal expression of STAT-3 (in cooperation
with T cells) was found to induce psoriasis-like lesions in
mice48. STAT-3 induced the upregulation of a number of genes relevant
for psoriasis, such as those encoding ICAM-1 and TGF-α; the latter
has been shown to stimulate proliferation of keratinocytes in psoriasis
via an autocrine loop. As STAT-3 is activated by a variety of cytokines
including IL-22 as well as IL-6, IL-20 and IFN-γ, this could represent
a link between keratinocyte activation and immune cells in the development
of the psoriatic lesion.
Topical Treatments
Guidelines of care for the treatment of psoriasis with topical therapies
have been developed by the American Academy of Dermatology64.
Vitamin D3 analogues
In the early 1990s, vitamin D3 analogues became commercially available
as a topical treatment for psoriasis. When the epidermis is hyperproliferative,
vitamin D3 inhibits epidermal proliferation, and it induces
normal differentiation by enhancing cornified envelope formation and
activating transglutaminase; it also inhibits several neutrophil functions.
Due to their therapeutic efficacy and limited toxicity, calcipotriene
(calcipotriol) and other vitamin D3 analogues have become a
first-line therapy for psoriasis65.
For a detailed description of topical vitamin D3 analogues, the reader
is referred to Chapter 129. Table 8.4 summarizes the major characteristics
of commercially available vitamin D3 analogues and Table 8.5
describes their indications and contraindications. Calcipotriene monotherapy
has been shown to result in a ~60% reduction of PASI after 8
weeks of treatment, but practical use in psoriasis patients usually
involves combination therapy with topical corticosteroids. When calcipotriene
and betamethasone dipropionate are combined, an ~70%
reduction in PASI has been observed (ointment formulation)66 as has
clearing/minimal disease in ~70% of patients with scalp psoriasis (gel
formulation)67.
Corticosteroids
Since their introduction in the early 1950s, topical corticosteroids
have become a mainstay in the treatment of psoriasis. They are often
first-line therapy in mild to moderate psoriasis and in sites such as the
flexures and genitalia, where other topical treatments can induce irritation. Chapter 125 provides
detailed information on mechanisms
of action, pharmacologic aspects and side effects of corticosteroid
therapy.
Corticosteroids are manufactured in various vehicles, from ointments,
creams and lotions to gels, foams and shampoos68; ointment
formulations, in general, have the highest efficacy (see Ch. 125). Over
the years, the anti-inflammatory properties of topical corticosteroids
have been improved by increasing their lipophilicity by masking the
hydrophilic 16- or 17-hydroxy groups or by introducing acetonides,
valerates or propionates. Application under plastic or hydrocolloid
occlusion also significantly enhances the penetration. Once-daily application
has been shown to be as effective as twice-daily application, and
long-term remissions may be maintained by applications on alternate
days69. The indications and contraindications regarding the use of
topical corticosteroids in the treatment of psoriasis are summarized in
Table 8.6.
At least 80% of patients treated with high-potency topical corticosteroids
experience clearance. In fact, the maximum improvement is
usually achieved within 2 weeks. With maintenance therapy consisting
of 12 weeks of intermittent applications of betamethasone dipropionate
ointment (restricted to weekends), 74% of patients remained in remission,
compared with 21% of the patients receiving a placebo ointment69.
Unfortunately, no efficacy data are available on prolonged treatment
for more than 3 months. As tachyphylaxis and/or rebound can occur
fairly rapidly, i.e. within a few days to weeks, intermittent treatment
schedules (e.g. once every 2 or 3 days or on weekends) are advised for
more prolonged treatment courses. Combination topical therapy can
take advantage of the rapid effect of topical corticosteroids as well as
the prolonged benefits of topical vitamin D3 analogues, anthralin or
retinoids.
Targeted immune modulators (“biologic” therapies)
Beginning in 2000, biologic therapies were introduced for the treatment
of psoriatic arthritis and moderate to severe psoriasis. Their two major
targets are T cells and cytokines, including TNF-α and IL-12/23. Table
8.16 lists the biologic agents that are currently commercially available.
Although briakinumab (a human monoclonal antibody against the p40
subunit of IL-12 and IL-23) was found to have greater efficacy than
methotrexate in patients with moderate to severe plaque psoriasis79a,
applications for approval by the FDA and European Medicines Agency
(EMEA) were withdrawn due to safety concerns (including a possible
increased risk of cardiovascular adverse events). Chapter 128 provides
a description of the modes of action, dosages, side effects and monitoring
recommendations for biologic agents. Of note, guidelines, including
European S3-Guidelines, have been developed for the treatment of
psoriasis patients with TNF-α inhibitors (adalimumab, etanercept and
infliximab) and ustekinumab74,80–82.
Biologic therapies are indicated for patients with moderate to severe
psoriasis and/or psoriatic arthritis. Several guidelines restrict their use
to “high-need patients” in whom all other existing treatments are contraindicated
or have led to insufficient improvement, whereas some
investigators have voiced the opinion that biologic therapies should be
an option for patients who have failed to respond adequately to one
classic systemic treatment83; the latter recommendation has to be balanced
against the high cost of these medications. Both indications and
contraindications for currently commercially available therapies are
outlined in Table 8.17.
The relative efficacies of the various biologic agents are reviewed in
Chapter 128. With regard to the percentage of patients achieving PASI
75 improvement, there is significant overlap between the efficacies of
biologic agents (as assessed after 3 months of therapy) and those of
photo(chemo)therapy and classic systemic medications such as MTX
and cyclosporine, although only a few studies directly comparing biologic
agents with classic systemic medications are available. In general,
TNF-α inhibitors and anti-IL-12/23 antibodies have substantial efficacy
and enable long-term control of psoriasis84.
Lichen planus.
Lichen ruber planus- a chronic dermatosis characterized by the appearance of the skin, less
frequently on oral mucosa, genitals, violet-colored papules with wax like brilliance. Etiology of
disease, immune-allergic, viral, infectious, neuroendocrine. Toxic-allergic, hereditary.
Pathomorphologic-hyperkeratosis, granulez, acanthosis, stripe infiltrate in the dermis,
penetrating into the epidermis (exocytose). There are acute and chronic forms.
Treatment-gipoallergic diet, hypnosis and electrosleep, sedation including bromide,
tranquilizers, anti-depressant.
Pityriasis rosea Gibert
Pink Zhiber lichen- infectious-allergic skin disease, characterized by a patchy rash. It is
infectious etiology of disease on the basis of positive intradermal reactions with streptococci
vaccine is not excluded viral genes. The disease often manifests itself in the background of ARI.
The clinic - occur among people 20-40 years of age, expressed seasonality of disease (the largest
number of cases in spring and autumn). The primary element in the form of disseminated rash of
small pink round or oval spots, reaching 1-2 cm in diameter.
Treatment - symptomatic.
Dermatitis, inflammation of the skin, caused by direct impact of various exogenous factors
and retrogressive in a few days, after the cessation of their effect on the skin. Depending on the
etiological factors are of dermatitis due to mechanical, physical, chemical factors of plants
(fitodermatity). Dermatitis Classification depending on the nature and mechanism of its irritant
action on skin: - simple or artifitsialny, dermatitis (or contact dermatitis), allergic dermatitis -
toxicodermia.
Clinic simple contact dermatitis depends on the irritant following parameters: strength and
concentration of the substance, duration of exposure. Etiological factor is a local irritant effect,
the incubation period, no. Localization of irritant action on the ground. For allergic dermatitis is
characterized by rash: - erythema, edema, papulosis and microvesicularis elements; moknutie;
crusts, squama.
Treatment
Because pityriasis rosea is often asymptomatic and self-limited, patient
education and reassurance represent a satisfactory treatment plan. In
patients with pruritus, counterirritant antipruritic lotions or low- to
medium-strength topical corticosteroids may be needed for symptomatic
relief. In more severe cases, UVB phototherapy (broadband
or narrowband) or natural sunlight exposure and oral antihistamines
can be used. Rarely, a brief course of systemic corticosteroids may
be required51.
In a double-blind, placebo-controlled trial, 73% of patients had complete
resolution after receiving 14 days of erythromycin in divided
doses52. The placebo group showed no resolution over the same time
period. In a bilateral comparison trial of UVB, a reduction in severity,
but not pruritus or duration, was observed53.
Atopic dermatitis
Although occurring at any age, atopic erythroderma develops most
frequently in patients with a history of moderate to severe atopic dermatitis.
As a result, well-established pre-existing lesions can be found,
especially when the erythroderma is of recent onset. The pruritus is
intense, and secondary excoriations or prurigo-like lesions are frequently
observed. Lichenification is often prominent and atrophy of the
skin due to topical corticosteroids may be seen. Increased serum IgE
and eosinophilia may accompany other signs and symptoms of atopy.
DIAGNOSTIC CRITERIA
Several authors and groups have suggested guidelines to assist in establishing
the clinical diagnosis of AD. Major features in these sets of
criteria include pruritus, eczematous skin lesions in typical age-specific
distribution patterns, a chronic or chronically relapsing course, early
age at onset, and a personal and/or family history of atopy. Atopic
stigmata (see Table 12.5), especially xerosis, are also recognized as supporting
features. The Diepgen score represents another validated set of
diagnostic criteria, which is separated into objective, subjective and
laboratory features49. Validated scores to assess the severity of AD
include the EASI (Eczema Area Scoring Index), SCORAD (SCORing
Atopic Dermatitis) and POEM (Patient-Oriented Eczema Measure)50.
IgE-associated and non-IgE-associated AD are distinguished based on
the evaluation of total serum IgE levels (elevated in the former; normal
<150 IU/ml) and the presence or absence of specific IgE. Although
recognition of the latter can support the diagnosis of an atopic state,
exposures to the allergens identified are not necessarily relevant to
aggravation of AD (see below).
TREATMENT
Because AD is a chronic relapsing disease, the classic approach to
therapy is targeting acute flares with short-term treatment regimens,
i.e. reactive management. Based on recent insights into the underlying
skin barrier defect and its relationship to inflammatory processes in
the skin and other organs, a proactive approach that includes long-term
maintenance therapy is now recommended51. Currently, management
of AD includes the following components:
_ avoidance of trigger factors, including irritants, relevant allergens
and microbial agents
_ skin care that aims to compensate for the genetically determined
impaired epidermal barrier function
_ anti-inflammatory therapy to control subclinical inflammation as
well as overt flares
_ in selected cases, adjunctive or complementary modalities.
As a rule, management should be adapted to the severity of the disease.
While mild cases can typically be controlled by continuous use of emollients
and intermittent use of a low-potency topical corticosteroid for
flares, moderate AD may also require proactive maintenance with antiinflammatory
agents. In more severe and refractory cases, the use of
phototherapy and systemic drugs may be necessary to control the
disease (Table 12.8). An appropriate educational program for patients
and parents is another essential component of the management of AD.
Drug reactions
The number of drugs that can cause erythroderma is staggering
(Table 10.3; see also Ch. 21). Whereas erythroderma resulting from
topical medications usually begins as dermatitis, eruptions due to systemic
drugs begin as a morbilliform or scarlatiniform exanthem. In
areas of greatest hydrostatic pressure (ankles and feet), the lesions may
become secondarily purpuric. Of the group of erythrodermas, those
that are drug-induced have the shortest duration, usually resolving
2–6 weeks after withdrawal of the responsible drug. However, it is
imperative to exclude a drug reaction with eosinophilia and systemic
symptoms (DRESS), nowadays often referred to as drug-induced hypersensitivity
syndrome (DIHS).
Allergic Contact Dermatitis
Many adverse events can occur when the skin comes in contact with
external agents. These reactions are varied, and include hyperpigmentation,
hypopigmentation, acne, urticaria, phototoxic reactions and
eczema. The eczema that is seen can be either allergic or irritant in
nature. Irritant contact dermatitis (ICD) accounts for approximately
80% of all contact dermatitis (see Ch. 15) and allergic contact dermatitis
(ACD) accounts for the remaining 20%1. ICD is the result of a
local toxic effect when the skin comes in contact with irritant chemicals
such as soaps, solvents, acids or alkalis. ACD is a delayed-type hypersensitivity
reaction that is elicited when the skin comes in contact with
a chemical to which an individual has previously been sensitized.
The cutaneous responses of ACD and ICD are dependent on the
particular chemical, the duration and nature of the contact, and individual
host susceptibility. The chemicals that cause contact dermatitis
are found in jewelry, personal care products, plants, topical medications
(prescription, over-the-counter or herbal) and home remedies, as well
as chemicals the individual comes in contact with at work, during
avocations or via contact with another individual (e.g. consort contact
dermatitis). The type of cutaneous reaction discussed in this chapter
is ACD.
ICD and ACD, especially the chronic forms, can take on similar
clinical appearances. The classic picture of contact dermatitis is a welldemarcated
erythematous vesicular and/or scaly patch or plaque with
well-defined margins corresponding to the area of contact (Fig. 14.1A).
The distribution can be linear, when an object such as a leaf or branch
is rubbed against the skin (Fig. 14.1B), or localized to the site where
there has been contact with the offending chemical or product, e.g.
hand dermatitis caused by ACD to gloves or foot dermatitis due to ACD
to shoes (Figs 14.2–14.4). Because ICD and ACD are not always discernible
clinically, patch testing is required to help identify an allergen
or exclude an allergy to a suspected allergen. Patch testing remains the
gold standard for diagnosing ACD.
Patients with the most common clinical presentations of ACD often
do not seek medical attention. Those who have earring dermatitis or
erythema and pruritus under a ring may simply diagnose themselves
as having an allergy to jewelry. An individual who is gardening over the
weekend may never present to a physician, because the “poison ivy
rash” is so familiar. Nickel (worldwide) and poison ivy (US; see Ch. 17)
are among the most common etiologies of ACD and are often not further investigated because
the cause is obvious. However, the clinical
picture and history are often not sufficiently specific to identify the
causative allergen, and patch testing is then necessary. For example,
the patient with chronic hand dermatitis or eyelid dermatitis who
comes to the office for treatment is often unaware that a personal care
product could be the cause of the problem. These are the patients who
can be most helped by a thorough history and cutaneous examination,
as well as the diagnostic procedure of patch testing.
ACD is an exciting field of interest within dermatology. It requires
an understanding of the disease process, the ability to recognize the
many ways in which ACD can present, a keen level of interest and an
appropriate level of suspicion for the possibility of an allergen, as well
as the ability to patch test, interpret, and educate patients on this
disease process. Hopefully, this chapter will raise interest and awareness
and help the reader come to a better understanding of these issues.
HISTORY OF PATCH TESTING
Jadassohn has been credited with describing the technique of patch
testing over 100 years ago. In 1931, Sulzberger and Wise2 formally
brought the technique to the US and described its use as a diagnostic
tool for identifying a causative allergen responsible for dermatitis. This
technique has been further developed over the years on a worldwide
basis, with standardized allergens, testing devices, and protocols.
Patch testing has remained the gold standard for diagnosing ACD.
However, despite the value of this diagnostic tool, studies have shown
that it is underutilized and not taught in many dermatology residency
programs, including those in the US3.
Patch Testing
Patch testing is a deceptively simple office procedure upon which the
diagnosis of ACD often rests. Although the procedure is straightforward,
deciding when and what to patch test requires training and
experience. Unfortunately, patch testing is still underutilized. Past
surveys have shown that only 50% of all residency programs in the US
have a patch test center, and 27% of the responders did no patch testing
at all3.
The TRUE Test®, which is approved by the US Food and Drug
Administration (FDA), consists of panels with pre-impregnated
(so-called “leave-on” products), such as moisturizers and make-up, may
be tested “as is”. Products that are intended to be diluted by water or
rinsed off (so-called “rinse-off” products), such as soaps and shampoos,
need to be diluted prior to patch testing. There are helpful guides for
determining appropriate patch test concentrations for numerous chemicals9.
When these non-standard allergens are tested, controls (including
vehicles) must be tested to evaluate for the possibility of ICD.
After allergen selection has been finalized, appropriate technique is
necessary to ensure adequate testing. The most common site is the
upper back. The patient should not have a sunburn in this area and
should not have applied topical corticosteroids to the sites of patch
testing for 1 week10,11. Systemic and longer-lasting injectable corticosteroids
should also be avoided for at least 1–2 weeks12. (If necessary
for disease control, the daily oral AM dose of corticosteroids should not
exceed the equivalent of 20 mg of prednisone during testing.) Any one
of these factors may decrease the individual’s ability to elicit a reaction
when challenged by an allergen, resulting in a false-negative test10–12.
A nurse or technician in the office can be trained to apply the patches,
and this leads to improved efficiency. Either the pre-packaged allergens
are placed on the back, as in the case of the TRUE Test®, or the allergens
are poured into Finn chambers (see Fig. 14.11) (Epitest Ltd,
Tuusula, Finland; available in the US from Allerderm Laboratories,
Inc.) that are adhered to Scanpor® tape (Norgeplaster, Vennesia, Norway;
available in the US from Allerderm Laboratories, Inc.) or IQ Chambers
™ (Chemotechnique® Diagnostics; distributed by Dormer Laboratories,
Inc.) and then applied to the back (Fig. 14.12). These patches
are then reinforced with more Scanpor® tape and the patient is sent
home with instructions to keep the back dry and the patches secured excessive sweating and to
avoid heavy lifting, as the patches may come
loose. Antihistamines can be prescribed, as they will not affect the
outcome of the testing. A map of where the allergens were placed
should be constructed for future reference.
When the patient returns at 48 hours, the patches need to be examined
to ensure that the testing technique was adequate. Initial inspection
can determine that the patches are still in place. Confirmation
comes from observing whether the chambers have adhered adequately
so as to leave an impression in the skin (see Fig. 14.14F). As the patches
are removed, their sites of application should be marked in order to
identify the location of the particular allergens (Fig. 14.13). Two types
of marking pen are recommended for this procedure: either a permanent
surgical marker or a fluorescent highlighter. Highlighters are less
messy and do not rub off as easily as the permanent marker. Because
of the latter property, permanent markers can soil clothing and make
interpretations at the second reading more difficult. Any positive reactions
are scored according to the International Grading System (Table
14.4; Fig. 14.14). The patient is again asked to keep the back dry until
the second reading, which can be performed from 72 hours to 1 week
after the initial application of patches.
When the patient returns for the second reading, the map is used to
identify any positive reactions. If a fluorescent marker has been utilized,
a Wood’s lamp may be needed to identify the markings. Positive reactions
are again graded according to the standard system.