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The psoriasiform reaction pattern is defined morphologically as the presence of epidermal hyperplasia with elongation of the rete ridges in a regular manner. This definition encompasses a heterogeneous group of dermatological conditions. This morphological concept is much broader than the pathogenetic one, outlined by Pinkus and Mehregan. They considered the principal features of the psoriasiform tissue reaction to be the formation of a suprapapillary exudate with parakeratosis, secondary to the intermittent release of serum and leukocytes from dilated blood vessels in the papillary dermis (the so-called “squirting papilla”).
The increased mitotic activity of the epidermis that results in the elongated rete ridges and the psoriasiform epidermal hyperplasia is presumed to be secondary to the release of various mediators from the dilated vessels in the papillary dermis in psoriasis. These aspects are discussed in further detail later. The epidermal hyperplasia in lichen simplex chronicus may be related to chronic rubbing and irritation, whereas in Bowen's disease there is increased mitotic activity of the component cells. In many of the conditions listed, the exact pathogenesis of the psoriasiform hyperplasia remains to be elucidated.
Psoriasis is the prototype of the psoriasiform reaction pattern, but note that early lesions of psoriasis and pustular psoriasis show no epidermal hyperplasia, although there is evidence of a “squirting papilla” in the form of dilated vessels and exocytosis of inflammatory cells with neutrophils collecting in the overlying parakeratotic scale.
The major psoriasiform dermatoses—psoriasis, psoriasiform keratosis, pustular psoriasis, Reiter's syndrome, pityriasis rubra pilaris, parapsoriasis and its variants, and lichen simplex chronicus—are considered first. The other dermatoses listed as causes of the psoriasiform reaction pattern have been discussed in detail in other chapters. They are included again here for completeness, with a brief outline of the features that distinguish them from the other psoriasiform dermatoses.
This group of dermatoses is characterized, as a rule, by regular epidermal hyperplasia, although in the early stages such features are usually absent. Psoriasis, which is the prototype for this tissue reaction, is considered first.
Psoriasis (psoriasis vulgaris) is a chronic, relapsing, papulosquamous dermatitis characterized by abnormal hyperproliferation of the epidermis. It affects approximately 2% of the population and involves all racial groups, although it is uncommon in Africans, South American Indians, and other indigenous people (Inuit, Aborigines, and Ami). Its incidence rate in a study from the United Kingdom was 14 per 10,000 person-years, whereas a prevalence rate of just greater than 1% was recorded in a Spanish study. Its incidence is high in Norway.
Psoriasis typically consists of well-circumscribed erythematous patches with a silvery white scale (plaque form). Characteristic bleeding points develop when the scale is removed. This has been called Auspitz's sign, although it appears that he has been wrongly credited with this observation. Pruritus is sometimes present. There is a predilection for the extensor surfaces of the extremities, including the elbows and knees, and also the sacral region, scalp, and nails. There is a broad spectrum of nail dystrophies associated with psoriasis, ranging from the common pitting, distal onycholysis, and loosening of the nail plate to the less common discoloration and splinter hemorrhages seen in the nail bed. Linear nail pitting and splinter hemorrhages are more common in psoriasis than in psoriatic arthritis. Subungual hyperkeratosis may also develop. Involvement of the palms and/or soles occurs in less than 20% of patients with psoriasis. A scarring alopecia is rare. The lips are not commonly involved, and oral lesions in the form of whitish areas on the mucosa are quite rare, but fissured tongue and geographic tongue are not uncommon and can be seen in both plaque-type and pustular psoriasis. Centrofacial involvement is a marker of severe disease. Penile lesions are more common in uncircumcised men. When psoriasis involves the anogenital region of women, vulvar scarring may ensue. Lesions may develop at sites of trauma and in peristomal skin.
In 5% or more of patients with psoriasis, a seronegative polyarthritis develops. Controversy exists as to whether they represent two related but different disease processes. A review has highlighted their overlapping etiology and pathogenesis. Achilles tendinitis is common in patients with psoriatic arthritis. Psoriatic onycho-pachydermo-periostitis (POPP) is a rare subset of psoriatic arthritis. Bilateral upper limb lymphedema has been reported in a patient with arthritis. Psoriasis has also been reported in association with obesity, vitiligo, gout, diabetes, ankylosing spondylitis, inflammatory linear verrucous epidermal nevus (ILVEN), HIV infection, benign migratory glossitis (geographic tongue), minor hair shaft abnormalities, gliadin antibodies, and inflammatory bowel disease, particularly Crohn's disease. Its association with bullous pemphigoid and other bullous diseases, perforating folliculitis, lupus erythematosus, Kawasaki disease, hyper–immunoglobulin E (IgE) syndrome, prolactinoma, Vogt–Koyanagi–Harada syndrome, insulinoma, CD4 + lymphocytopenia, Laurence–Moon–Biedl syndrome, epidermal nevi, multiple exostoses, and surgical scars is probably a chance occurrence. Some studies have shown an elevated risk of malignancy in patients with psoriasis, especially among younger and male patients. A statistically significant relationship has been found between psoriasis and colon cancer. There is a slight increase in the incidence of lymphoma and carcinoma of the larynx in patients with psoriasis, which is unrelated to mode of treatment. Patients with psoriasis are more likely to have one or more autoimmune diseases, the strongest association being with rheumatoid arthritis. Psoriasiform eruptions may be a paraneoplastic phenomenon. Heart disease appears to be increased in patients with psoriasis, as a consequence of increased atherosclerosis. This may be a consequence of significantly decreased levels of high-density lipoproteins. Serum leptin levels are increased in patients with psoriasis. Patients show signs of insulin resistance. Severe but not mild psoriasis is associated with an increased risk of death.
The mean age of onset of psoriasis is approximately 25 years, although it also develops sporadically in older persons, in whom it tends to have a milder course. Childhood cases are not uncommon, particularly in Scandinavia, where the disease commences in childhood in a high proportion of cases. Plaque psoriasis is the most common type in childhood. In those younger than 2 years of age, a psoriatic diaper rash with dissemination is the most common type. Congenital onset is a rare occurrence. A family history of psoriasis and an association with HLA-Cw6 are often present in those with early onset.
Facial involvement, nail involvement, and Koebner reactions are more common in early-onset psoriasis. Psoriasis usually runs a chronic course, although spontaneous or treatment-induced remissions may occur. Its spontaneous clearance during the course of Kikuchi's disease has been reported. It can have a significant effect on the quality of life in those persons with the disease. Patients with palmoplantar psoriasis have more disability and discomfort than patients with other forms of psoriasis. To assess the effects of treatment on psoriasis, various indices of severity and area of involvement have been devised.
Several clinical variants of psoriasis have been recognized. Guttate psoriasis consists of 1- to 5-mm erythematous papules, which eventually develop a fine scale. It may be preceded by a streptococcal pharyngitis. Evidence of a preceding streptococcal infection is found in approximately two-thirds of cases of guttate psoriasis. T lymphocytes specific for group A streptococcal antigens have been isolated from lesions of guttate psoriasis. There is a predilection for the trunk, and it is more common in children. Clearing may occur spontaneously in weeks or months. Psoriasis begins as the guttate form in 15% or more of cases. It appears that a subset of patients with guttate psoriasis undergo complete or long-term remission, whereas another group has a chronic course, without remission and with progression to chronic plaque psoriasis. Among the former, there is an earlier age of onset with high ASO titers, whereas the latter tend to have a somewhat later age of onset and a family history of psoriasis. Erythrodermic psoriasis develops in approximately 2% of patients with psoriasis, and it accounts for 20% or more of erythrodermas. It is a severe form involving more than 90% of the skin with a high morbidity and an unpredictable course. A verrucous form of erythrodermic psoriasis has been described. Erythrodermic psoriasis may be precipitated by administration of systemic steroids, by the excess use of topical steroids, by radiological contrast media, or by a preceding illness; it may develop as a complication of phototherapy. Peripheral blood eosinophilia may be present in this form. Sebopsoriasis consists of yellowish-red, less well-marginated lesions, with variable degrees of scaling, often distributed in seborrheic regions of the body. Rare clinical variants include a nevoid form, sometimes along the lines of Blaschko, photosensitive psoriasis, inverse (flexural) psoriasis, follicular psoriasis, psoriasis spinulosa, psoriasis bullosa acquisita, congenital erythrodermic psoriasis, interdigital psoriasis, rupioid psoriasis, annular plaque-type psoriasis, annular verrucous psoriasis, verrucous (hypertrophic) psoriasis, erythema gyratum repens–like psoriasis, erythema annulare centrifugum-type psoriasis, and linear psoriasis, although the occurrence of a linear form of psoriasis is not accepted by some authorities. Linear psoriasis can be superimposed upon other forms of the disease and may reflect a clone of cells harboring a postzygotic mutation. Psoriasiform napkin dermatitis may also be a variant of psoriasis. Pustular psoriasis is regarded as a discrete entity. Different forms of the disease may alter their morphology and become a different clinical type. This phenotype switching may be a consequence of alterations in interleukin pathways.
Cases reported as psoriasiform acral dermatitis are now thought to represent a variant of psoriasis in children and not a discrete entity. This variant is characterized by cutaneous involvement of the digits without nail dystrophy.
There is a genetic proclivity to psoriasis, but no precise mode of inheritance is clear. The pattern is polygenetic rather than single-gene inheritance. A recessive mode of inheritance has been suggested in Swedish patients. Concordance in monozygotic twins varies from 35% to 70% or more. It is 15% to 30% in dizygotic twins. These statistics suggest that non-shared environmental influences also play a role.
Since 1994, many genetic loci (mainly on chromosomes 17q, 4q, 2p, 1q, and 6p) comprising at least nine genes have been under investigation. At least 19 different putative loci for genetic susceptibility to psoriasis have been reported. Recent studies suggest that there is a major susceptibility region for psoriasis on chromosome 6p21.3, near to HLA-C. It has been estimated that the proportion of genetic susceptibility attributable to this gene (PSORS1C3) is approximately 30%. Attempts to link this gene to the CDSN gene (corneodesmosin), also near to HLA-C, were initially unsuccessful. Both genes as well as the nearby HCR gene are now regarded as important psoriasis susceptibility genes in Chinese patients with psoriasis, although this has been questioned. The CDSN gene is associated with psoriasis vulgaris in Caucasian but not in Japanese populations. However, PSORS1 shows epistasis with genes at other locations, such as on 1p. PSORS1 contains several genes, some of which have an association with psoriasis. Another study of psoriasis in Chinese patients suggested that the MICA gene, another HLA-related gene on chromosome 6p21.3, may be a candidate gene. The ACE gene variants may confer susceptibility in some populations. The leptin gene did not appear to be involved in a Turkish population. Promoter region polymorphisms in the tumor necrosis factor α (TNF-α) gene have been associated with early-onset psoriasis in a Polish population but not in Japanese, Chinese, or Korean people. In contrast, IL12B gene polymorphisms, another cytokine gene, did confer a risk for psoriasis vulgaris in several different populations. Polymorphisms in the PTPN22 region are associated with psoriasis of early onset. Other proinflammatory genes have also been implicated. Recent studies have resulted in an increase in the number of candidate genes in psoriasis and psoriatic arthritis cohorts, which can be grouped into signaling networks affecting skin barrier function ( LCE3 , DEFB4 , and GJB2 ), innate immune responses involving nuclear factor κB ( NFKB ) and interferon signaling ( TNFAIP3 , TNIP1 , NFKBIA , REL , FBXL19 , TYK2 , and NOS2 ), and adaptive immune responses connected with CD8 + T cells and interleukin-23 and -17 (IL-23/IL-17)–mediated lymphocyte signaling ( HLA-C , IL12B , IL23R , IL23A , TRAF3IP2 , and ERAP1 ). A recent review of the complex subject of the genetics of psoriasis has been published.
Psoriasis is associated with HLA-Cw6, B13 and B17 on serology, and specifically with HLA-Cw*0602, HLA-DQA1*0104, and HLA-DRB1*0701 by polymerase chain reaction. An early study showed that all patients with guttate psoriasis carried the HLA-C allele, compared with 20% of the control population. This has not been confirmed by a subsequent study that concluded that the role of this allele in psoriasis has yet to be determined. In a recent report of severe erythrodermic psoriasis in twins, the major histocompatibility complex class I, Cw*06 was detected in both. It has been suggested that PSORS1 may indeed be the HLA-CW*06 allele encoding the HLA-CW6 molecule.
MicroRNAs (mi-RNAs) are implicated in the pathogenesis of psoriasis and also atopic eczema. Their effects may be mediated through a number of secondary pathways, including the TNF-α pathway. An imbalanced miRNA axis has been delineated in the pathogenesis of psoriasis, in which there is upregulation of miR-31/miR-203 and downregulation of hsa-miR99a/miR-125b.
Specific factors may trigger the onset or exacerbation of psoriasis. Trauma, infections, and drugs are accepted triggers, whereas the roles of climate, hormonal factors, cigarette smoking, alcohol, mesotherapy, internal malignancy, and stress are sometimes disputed. Vitamin D has immunomodulatory effects on psoriasis. In a study of patients in the Mediterranean region it has been shown that, among psoriatic patients, insufficient intake of vitamin D is associated with a greater risk of dyslipidemia, metabolic syndrome, and cardiovascular comorbidity than is the case in normal controls who are also vitamin D deficient. Psoriasis may actually improve during pregnancy. It is often worse in the postpartum period. The development of lesions in response to trauma (Koebner reaction) is present in approximately one-third of cases. A link has been made between psoriasis and human papillomaviruses (HPVs) specifically associated with epidermodysplasia verruciformis, particularly the oncogenic HPV-5. The prevalence of HPV in hairs plucked from patients with psoriasis is increased in patients treated with psoralen-UV-A (PUVA). However, one study did not find a specific causal role for HPV-5 or HPV-36 in the pathogenesis of psoriasis. The role of Malassezia is more controversial. The improvement of scalp psoriasis treated with antifungal agents has suggested a role for Malassezia . Malassezia restricta is the predominant species in psoriatic scale. Malassezia globosa is also increased, but much less so. Cell wall–deficient bacterial infection may be a triggering factor through its effect on T-cell activation. Infection may precipitate guttate psoriasis. Drugs that precipitate or exacerbate psoriasis are listed in Table 5.1 . It has been suggested that the eruptions produced by TNF-α agonists may be a “new model of adverse drug reaction” rather than true psoriasis because the histology shows lichenoid and spongiotic features. The eruption triggered by efalizumab, a human anti-CD11a monoclonal antibody used in the treatment of psoriasis, consists of new papular lesions that arise in previously unaffected areas. They usually do not necessitate termination of efalizumab therapy and may optionally be treated with corticosteroids. A psoriasiform eruption, as opposed to true psoriasis, has been reported as a complication of several β-blocker drugs, and the related propafenone, with fluorescein sodium used in angiography, with the oral hypoglycemic agent glibenclamide, with icodextrin, and with terbinafine (discussed previously). The reactions caused by some of the β-blocker drugs have a lichenoid histology despite their clinical appearance. Psoriasis has also followed the use of stem cell transplantation.
|Calcium channel blockers||Icodextrin||Radioactive iodine|
Psoriasis is a complex disease in which numerous abnormal findings have been reported. Despite this, the primary (initiating) alteration is unknown, but it appears that the molecular phenotype necessary for the clinical expression of psoriasis is present in all keratinocytes and includes a capacity for hyperproliferation and altered differentiation. Control of the expression of this phenotype involves the keratinocytes as well as cells of the immune system and various cytokines. Many of the changes in these elements may be epiphenomena or secondary and tertiary events in the pathogenetic cascade. As mentioned previously, the primary alteration is not known, although it may involve the signal-transducing system of epidermal keratinocytes or the transcription regulatory elements associated with one or more cytokines. Stimulation of the immune system by superantigens has also been put forward as a primary event (see later). It is possible that different etiologies may initiate psoriasis in the genetically susceptible individual. Various aspects of the pathogenesis of psoriasis, particularly the immunopathogenesis, have been reviewed.
Because the earliest detectable morphological change in psoriasis involves blood vessels in the papillary dermis, some research has focused on their role in the pathogenetic cascade. Vascular changes in psoriasis include dilatation and tortuosity of vessels in the papillary dermis, as well as angiogenesis (neovascularization) and the formation of high endothelial venules, which are specialized postcapillary venules lined by tall columnar or cuboidal endothelial cells. These factors are important in expanding the size of the microcirculation that may, in turn, facilitate the trafficking of T lymphocytes, of the T helper 1 (Th1) subclass, into the skin, thus maintaining the psoriatic plaque. Blood flow is increased in these plaques. The high endothelial venules play an important role in the cutaneous recruitment of circulating lymphocytes. Microvascular hyperpermeability is another feature of severe psoriasis. This appears to be mediated by circulating vascular endothelial growth factor (VEGF). Angiogenesis is stimulated by factors such as IL-8 and transforming growth factor α (TGF-α). The presence of angiogenesis in psoriasis has been challenged. Using three-dimensional reconstructions, it has been suggested that downgrowths of the rete ridges include the vessels of the horizontal plexus, giving the appearance of intrapapillary capillaries. This study has not been confirmed. In short, it appears that dermal capillary changes alone are unlikely to be causal in psoriasis.
Recruitment of lymphocytes to the papillary dermis is an important factor. This is aided by various chemoattractants such as platelet-activating factor and leukotriene B 4 . Some of these lymphocytes are already activated before entering the skin, while still circulating in the bloodstream. The lymphocytes bind to endothelial cells in venules in the papillary dermis as a consequence of the enhanced expression of various adhesion molecules by endothelial cells. It appears that lymphocyte function–associated antigen type 1 (LFA-1), consisting of CD11a and CD18 subunits, which acts as a ligand for intercellular adhesion molecule 1 (ICAM-1), and ICAM-1 itself play a major role in the adhesion of CD4 + T cells to endothelial cells. Furthermore, TNF-α may play an important role in induction of adhesion molecules on endothelial cells. Vascular adhesion protein 1 (VAP-1) is also overexpressed in psoriasis. Efalizumab, an anti-CD11a antibody, has been used to treat psoriasis (see later). Lymphocytes then diapedese transendothelially and pass through the vessel wall into the papillary dermis. Neutrophils will subsequently leave the vessels in a similar way and migrate into the stratum corneum. Chemotactic factors such as C5a anaphylatoxin are important in their recruitment.
Whereas the importance of T lymphocytes in the pathogenesis of psoriasis is accepted, there has been some dispute regarding the relative importance of CD4 + and CD8 + lymphocytes. The T cells in lesional dermis are predominantly CD4 + . Cells migrating into the epidermis are mostly CD8 + . Which type produces keratinocyte proliferation by the release of mediators (cytokines) is still disputed. Recent work indicates that CD4 + cells are most important in some tissues, but the CD4/CD8 ratio is reversed in the epidermis, synovial fluid, and entheses (connective tissues between tendon or ligament and bone), where CD8 + cells are more common. In fact, the classic microscopic changes of psoriasis are associated with CD3 + T-cell infiltrates and epidermotropism of CD8 + cells. Both now appear to be involved, but CD8 + cells are particularly important. CD8 + cells in the epidermis express the Vβ T-cell receptor subgroups Vβ3 and Vβ13.1. Another study has shown an increase in the Vβ2 receptor in skin-homing lymphocytes in psoriasis. In psoriasis, CD4 + CD25 + regulatory T cells are functionally deficient in suppressing effector T-cell proliferation.
Recent work has focused on a subset of γδ T cells that reside in the dermis. These cells are a major source of IL-17 in skin after IL-23 stimulation (see the following discussion) and are believed to play a role in the pathogenesis of psoriasis. As mentioned previously, leukocytes bind to endothelial cells in the papillary dermis, before their passage from the vessels. This process is under the control of adhesion molecules, which can be classified into three distinct groups:
The immunoglobulin gene superfamily, which includes ICAM-1 (CD54) and ICAM-2 and vascular cell adhesion molecule 1 (VCAM-1)
Selectins (the most important of which is E-selectin)
One or more of these adhesion molecules lead to the selective adhesion of CD4, CD45RO helper T cells. Other categories of adhesion regulators, such as the proline-directed serine/threonine kinases, of which CDK5 is a member, exist. They appear to influence cadherins and integrins. The expression of CDK5 is reduced in psoriasis. Various cytokines appear to induce the enhanced expression of these adhesion molecules in psoriasis; they include IL-1, IL-2, TNF-α, interferon-γ (IFN-γ), and IL-4. On the other hand, UV-B radiation reduces the adhesive interactions and expression of adhesion molecules, possibly explaining its mode of action in the treatment of psoriasis. Serum levels of soluble E-selectin correlate with the extent of psoriatic lesions.
There is a complex interplay between the various cytokines found in the skin in psoriasis; some cytokines have more than one action. They are produced mostly by lymphocytes, although keratinocytes release at least two. Dendritic cells and macrophages also produce important cytokines, one of which is IL-12. IL-12 induces differentiation of naive CD4 T lymphocytes to Th1 cells, which are key effector cells in the pathogenesis of psoriasis as a consequence of their production of various cytokines such as IFN-γ and IL-2. It also activates natural killer cells. IL-23, which is closely related to IL-12 in structure, stimulates a subset of CD4 + lymphocytes to produce IL-17. The importance of IL-17 has been emphasized in recent years, as it has become evident that Th17 cells play a significant role as proximal regulators of inflammation in psoriatic skin. IL-17A, the main effector cytokine of Th17 cells, induces the production of proinflammatory cytokines, predominantly by endothelial cells and macrophages, and other molecules to sustain chronic inflammation. Serum β-defensin 2 (BD-2) is an easily measurable biomarker of IL-17A activity. Not surprisingly, the inhibition of IL-17A has been considered a potential treatment approach for disrupting the cycle of psoriatic inflammation.
Therapy using an IL-12/IL-23 antibody has undergone clinical trials (see later). IL-18, a novel cytokine produced mainly by monocytes and macrophages but also synthesized by keratinocytes, plays an important role in the Th1 response by stimulating the production of IFN-γ and TNF. It is increased in the serum of patients with psoriasis. In contrast, low levels of IL-10, an antiinflammatory cytokine, have been found in psoriatic lesions. The many functions of these various cytokines include stimulation of keratinocytes, vascular changes (discussed previously), control of lymphocyte trafficking (discussed previously), and stimulation of neutrophil chemotaxis. Exacerbations of psoriasis are preceded by a rapid increase in neutrophil chemotaxis. IL-8 is a cytokine with possibly more chemotactic activity than the various complement factors. Another is psoriasin (S100A7), a protein belonging to the calcium-binding S100 family. It is a potent inflammatory mediator. Two other members of this family, S100A8 and S100A9, are increased in psoriasis and contribute to the hyperproliferation of psoriatic skin. The importance of the cytokines in the pathogenesis is shown by the downregulatory effects of cyclosporine (ciclosporin) on cytokines and cytokine receptors in the treatment of psoriasis. The role of the various cytokines in psoriasis has been reviewed. They are summarized in Table 5.2 .
|Pathogenetic cascade||Cytokines involved|
|Endothelial activation and vascular changes||→||IL-1, IL-6, IL-8, TNF-α, TGF-α/β, IFN-γ, endothelin-1|
|Lymphocyte recruitment||→||IL-1, IL-8, MCP-1, TNF-α, psoriasin, CD11a/CD18 (LFA-1), ICAM-1|
|Keratinocyte–lymphocyte interactions||→||IL-1, IL-7, IL-8, TNF-α, IFN-γ, CD11a/CD18|
|Amplification of inflammatory mechanisms||→||IL-1, IL-2, IL-6, IL-8, IL-12, IL-17, IL-18, IL-23, TNF-α, IFN-γ, amphiregulin, MCP-1 (IL-10 is antiinflammatory)|
|Keratinocyte proliferation||→||IL-1, IL-3, IL-6, IL-8, GM-CSF, IFN-γ, TGF-α, EGF, TNF-α, amphiregulin, endothelin-1, insulin growth factor, TGF-β receptors, GRO-α, phospholipase C/protein kinase C system, S100A8, S100A9|
The final pathway in the pathogenesis of psoriasis involves the stimulation of keratinocytes by factors such as TNF-α, IL-6, IL-8, TGF-α, IFN-γ, granulocyte/macrophage colony-stimulating factor, and the phospholipase C/protein kinase C signal transduction system (see later). IFN-γ, which plays an important role in the growth stimulation of keratinocyte stem cells in psoriasis, can be produced by mast cells as well as lymphocytes. TNF-α also has a major role. Its release from cells is under the influence of TNF-α-converting enzyme (TACE). The success of the various TNF-α neutralizing modalities in the treatment of psoriasis has led to a reevaluation of the role of TNF-α in the pathogenesis of psoriasis. It seems likely that dysregulation of innate immunity, involving natural killer (NK) T cells, plays a role in the pathogenesis of psoriasis. This is supported by the finding of increased levels of perforin, the cytotoxic product of NK cells, in the epidermis of psoriatic plaques. Paradoxically, circulating NK cells are reduced in psoriasis. There is also an overexpression of the CXC chemokines, IL-8, and growth-regulated oncogene (GRO)/melanoma growth-stimulatory activity (GRO-α/MGSA). They are potent activators of neutrophils and lymphocytes but also stimulate proliferation of keratinocytes. These factors produce an alteration in the turnover time for the epidermis: 3 or 4 days in psoriasis compared with the usual 13 days in normal skin. It has been estimated that there is a 12-fold increase in the number of basal and suprabasal keratinocytes in cell cycling. TGF-β, which is elevated in psoriasis, is predominantly synthesized in subcorneal keratinocytes. It is a potent mitogen that can also stimulate angiogenesis. In contrast, TGF-β has an inhibitory effect on epithelial cell proliferation. Downregulation of its receptor in psoriatic epidermis has the effect of diminishing this inhibitory influence. Amphiregulin, a cytokine that acts as an epidermal growth factor, is also increased in psoriatic keratinocytes. Transgenic mice engineered to overproduce amphiregulin develop a psoriasis-like phenotype, suggesting that a genetically transmitted alteration of amphiregulin synthesis may be a possible cause of the cascade of events in psoriasis. There is increased activation of the Src family of tyrosine kinases (SFKs) in psoriasis. They are important regulators of epidermal growth and differentiation. The existence of an increased number of epidermal growth factor receptors (EGF-Rs), resulting from their persistence at all levels of the epidermis instead of just the basal layer, may be just as important. Antigen-presenting cells expressing the common heat shock protein receptor CD91 have been found juxtaposed to keratinocytes expressing HSP70, a ligand for CD91 in a mouse model of psoriasis. These activated antigen-presenting cells produce TNF-α in close proximity to these keratinocytes. T-cadherin, E-cadherin, P-cadherin, and protein kinase D expression all seem to play a part in the regulation of epidermal growth in psoriasis. Associated with this hyperproliferation of keratinocytes is a mild increase in apoptosis and a reduction in the number of Bcl-2–positive cells in the basal layer. Bcl-2 expression in lymphocytes is increased. Suppression of apoptosis also occurs in psoriasis. Survivin, a member of the inhibitor of apoptosis protein (IAP) family, is increased in psoriasis. It appears to be regulated by the transcriptional factor NF-κB. Some of the therapies for psoriasis act by their increase in apoptosis. A senescence switch involving p16 may prevent malignant transformation of this upregulated epidermis. Also, methylation of the p16 INK4 gene promoter is found in psoriatic epidermis.
As a consequence of the hyperproliferation of keratinocytes, there is enhanced expression of keratins K6, K16, and K17 and reduced amounts of the keratins indicative of differentiation (K1, K2, and K10). K16 is also expressed in nonlesional psoriatic skin and may serve as a marker of preclinical psoriasis. It has been found that altered peptide ligands derived from keratin 17 are capable of inhibiting proliferative responses of psoriatic T cells and keratinocyte proliferation in vitro . This opens up another therapeutic option in the treatment of psoriasis. There is a unique subpopulation of cells in psoriatic epidermis that coexpress K6 and K10. There is also increased nuclear β-catenin in suprabasal cells, alterations in cell-surface glycoconjugates, and variations in the epidermal differentiation complex—a cluster of genes on chromosome 1q21 that fulfill important functions in the terminal differentiation in the human epidermis. Tight junction components are also altered. It has also been suggested that basement membrane laminin could be important in driving psoriasis, at least in part through a T-cell–mediated immune response.
The role of microbiological superantigens in the pathogenesis of psoriasis is gaining acceptance, although formal proof of a pathogenic role is still lacking. Superantigens are toxins of microbial origin that not only stimulate certain classes of T cells but also have the capability to interact directly (without prior processing) with MHC class II molecules; this leads to considerable T-cell activation and cytokine release. Streptococcal antigens can function as superantigens, and it is suggested that they may act as the initiating factor in some cases of guttate psoriasis, in part through superantigen-driven generation of Vβ-restricted CLA-positive skin-homing lymphocytes. One study has confirmed that prior pharyngeal infection is a risk factor for guttate psoriasis. Peripheral blood lymphocytes from patients with psoriasis are generally hyporesponsive to streptococcal superantigens, but there is a subpopulation of CD4 + cells that produces IFN-γ in response to this antigen. Superantigens produced by Staphylococcus aureus may also be triggering factors. Malassezia furfur is also capable of exacerbating psoriasis. Patients with psoriasis harbor HPV-5 in a significant number of cases. Antibodies to HPV-5, one of the types associated with epidermodysplasia verruciformis, appear to be generated in the epidermal repair process, but whether they contribute to a proliferation of keratinocytes in psoriasis is not known. The high prevalence of cytomegalovirus antigenemia in psoriasis is possibly related to reactivation of the virus by elevated levels of TNF-α. Endogenous retroviral sequences are expressed in psoriasis. They are part of the normal human genome. Their possible role in the pathogenesis of psoriasis is currently being investigated. It has been suggested that a broad range of viral and bacterial stimuli may stimulate psoriasis, not by acting on T cells directly but by stimulating plasmacytoid dendritic cells (myeloid-derived cells) to produce large amounts of type 1 interferons (IFN-α/β).
These disparate findings remain to be integrated into a unitarian theory of pathogenesis. It is possible that abnormalities in epidermal barrier function play a role in the pathogenesis of psoriasis, as is the case for a number of other disorders, such as Crohn's disease, that are considered “barrier organ disorders.” A number of highly conserved genes—particularly nucleotide-binding domain, leucine-rich containing (NLR), or CATTERPILLER genes—are associated with barrier organs such as skin and contribute to the defense against microbial pathogens; the discovery of defects in this system in psoriasis could lead to novel therapeutic approaches. Other findings in psoriasis that may play some role in the pathogenetic cascade include the increased expression of heat shock proteins by keratinocytes, an increase in reactive oxygen species, excessive activation of a phospholipase C/protein kinase C signal transduction system that stimulates keratinocyte proliferation, overexpression of serpin squamous cell carcinoma antigens in psoriatic skin, and increased lysophosphatidyl choline activity in lesional skin. This substance is a lysophospholipid that is chemotactic for monocytes and stimulates the expression of certain adhesion molecules—VCAM-1 and ICAM-1. The finding of immunoreactants in the stratum corneum and the dermis is not thought to be of major pathogenetic significance. There is an upregulation of the gap junction protein connexin 26 between keratinocytes of psoriasis. There is also an overexpression of matrix metalloproteinases 2 (MMP-2) and 9 (MMP-9) and other related members of the ADAM family. Increased levels of kallikreins are also found in the stratum corneum and serum of patients with psoriasis. Telomerase activity is increased in peripheral blood mononuclear cells in psoriasis. The level correlates with disease severity. There is also increased expression of the natural killer cell inhibitory receptor CD94/NKG2A and CD158b on circulating and lesional T cells in psoriasis, and this elevation correlates with disease severity. The significance of these findings is uncertain. Increased levels of elafin, also termed skin-derived anti-leukoproteinase (SKALP), are found in subcorneal keratinocytes of psoriatic lesions. It is a potent elastase inhibitor that may protect the epidermis from the proteolytic activity of neutrophils. The epidermis is also protected against bacterial infections by the release of granulysin by lesional T cells and dendrocytes. The exact role of neuropeptides (including substance P) remains to be clarified. They provide a possible explanation for the triggering action of stress in the exacerbation of psoriasis. Increased serum cortisol levels are another possible mechanism by which stress influences psoriasis. Serotonin levels are also increased in the lesions of psoriasis.
In concluding this section, it should not be forgotten that psoriasis is characterized by erythematosquamous lesions. The erythematous nature of the lesions results from the dilatation and increase in vessels in the dermal papillae, which have a thin, overlying layer of epidermal keratinocytes. The clinical thickening of the lesions results from the psoriasiform epidermal hyperplasia brought about by increased mitotic activity in basal keratinocytes through the action of various cytokines with growth factor activity. The scale is composed of parakeratotic cells, resulting from increased transit time, and a focal admixture of neutrophils. All of these features are possibly the consequence of an autoreactive inflammatory process mediated by T lymphocytes of the Th1 subclass. This cytokine profile may be the result of local factors and not determined by a specific genotype.
Guttate psoriasis is managed with tar and UV-B therapy (with questionable efficacy), dithranol and topical corticosteroids with or without UV-B therapy, or calcipotriol (also a useful agent in other forms of psoriasis). Whereas antistreptococcal therapy is generally not effective in the management of guttate or plaque psoriasis, tonsillectomy may be beneficial in select patients who have recurrent streptococcal infections. Other therapies used in psoriasis include topical corticosteroids, most often used in tandem with other agents, calcineurin inhibitors, PUVA, narrowband UV-B, saltwater baths with UV-B irradiation (balneophototherapy), systemic retinoids, methotrexate, cyclosporine, tacrolimus, mycophenolate mofetil, hydroxyurea, 6-thioguanine, sulfasalazine, efalizumab (a CD11a blocker), TNF-α antagonists etanercept, infliximab, and adalimumab, and alefacept, an agent that reduces CD45RO-positive T cells. Newer treatments include the recombinant IL-10 agent ilodecakin, ABT-874 (an IL-12/23 monoclonal antibody), botulinum toxin type A for flexural psoriasis, oral bexarotene, a synthetic retinoid X receptor, paclitaxel, everolimus, a rapamycin-derived macrolide, the thiazolidinediones, new-generation, all- trans retinoic acid metabolism blocking agents (RAMBAs), dimethylfumarate, teneligliptin and sitagliptin (members of a new class of antidiabetic agents with immunomodulating properties), and secukinumab, brodalumab, and ixekizumab (new biological agents that target IL-17).
Psoriasis is a dynamic process and consequently the histopathological changes vary during the evolution and subsequent resolution of individual lesions. The earliest changes, seen in lesions of less than 24 hours’ duration, consist of dilatation and congestion of vessels in the papillary dermis and a mild, perivascular, lymphocytic infiltrate, with some adjacent edema. There is also some exocytosis of lymphocytes into the epidermis overlying the vessels, and this is usually associated with mild spongiosis ( Fig. 5.1 ). The epidermis is otherwise normal. This is soon followed by the formation of mounds of parakeratosis, with exocytosis of neutrophils through the epidermis to reach the summits of these parakeratotic foci. There is often overlying orthokeratosis of normal basket-weave type and loss of the underlying granular layer. At this papular stage, increased mitotic activity can be seen in the basal layer of the epidermis associated with a modest amount of psoriasiform acanthosis ( Fig. 5.2 ). Keratinocytes in the upper epidermis show some cytoplasmic pallor. Blood vessels in the papillary dermis are still dilated and somewhat tortuous, and their lumen may contain neutrophils. Lymphatic channels are also increased. Very few neutrophils are ever present in the perivascular infiltrate; this consists mainly of lymphocytes, Langerhans cells, and indeterminate cells. A few extravasated erythrocytes may also be present. These changes can also be seen in guttate psoriasis, although the epidermal hyperplasia is usually mild in this variant of psoriasis.
In early plaques of psoriasis and in “hot spots” of more established plaques, there are mounds of parakeratosis containing neutrophils, which usually migrate to the upper layers (summits) of these mounds ( Fig. 5.3 ). With time, confluent parakeratosis develops ( Fig. 5.4 ). Several layers of parakeratosis containing neutrophils, with intervening layers of orthokeratosis, are sometimes present. Although intracorneal collections of neutrophils (Munro microabscesses) are common, similar collections in the spinous layer (spongiform pustules of Kogoj) are less so. They are also much smaller than in pustular psoriasis. Munro microabscess can also be detected by reflectance confocal laser microscopy, a noninvasive technique that can also be used to demonstrate parakeratosis and tortuous papillary dermal capillaries (see later). These pustules contain lymphocytes in addition to neutrophils. The epidermis now shows psoriasiform (regular) hyperplasia, with relatively thin suprapapillary plates overlying the dilated vessels of the papillary dermis ( Fig. 5.5A ). Ki-67 expression is increased. A few mononuclear cells are usually present in the lower layers of the suprapapillary epidermis. The dermal inflammatory cell infiltrate is usually slightly heavier than in earlier lesions. It includes activated T lymphocytes, fewer Langerhans cells than in earlier lesions, and very occasional neutrophils. A subset of spindle-shaped macrophages, situated along the basement membrane, has been described as a characteristic feature. These so-called “lining cells” are positive for CD11c. There are increased numbers of dermal macrophages in psoriatic skin, a number of these being CD163 positive; these probably contribute to the pathogenesis of the disease through the release of inflammatory mediators. Plasma cells and eosinophils are usually absent, but eosinophil cationic protein has been identified, particularly in the upper third of the epidermis in psoriasis. Plasma cells may be present in patients with HIV infection.
With time, there may be club-shaped thickening of the lower rete pegs with coalescence of these in some areas ( Fig. 5.5B ). Later lesions show orthokeratosis, an intact granular layer, and some thickening of the suprapapillary plates. Exocytosis of inflammatory cells is usually mild. The finding of numerous fatty vacuoles in the papillary dermis—pseudolipomatosis cutis (see p. 1071 )—is of doubtful significance. The phenomenon has not been satisfactorily explained. If psoriatic plaques are rubbed or scratched, the histopathological features of the underlying psoriasis may be obscured by these superimposed changes.
The term psoriatic neurodermatitis has been proposed for pruritic, lichenified plaques on the elbows and/or knees. Lesions were more numerous, smaller, more keratotic, and less excoriated than in typical lichen simplex chronicus. Microscopically, the lesions showed microabscesses in the horny layer, hypogranulosis, regular acanthosis, and thinning of the suprapapillary plates. It is thought that these cases represent psoriasis with superimposed lichen simplex chronicus.
In resolving or treated plaques of psoriasis, there is a progressive diminution in the inflammatory infiltrate, a reduction in the amount of epidermal hyperplasia, and restoration of the granular layer. Vessels in the papillary dermis are still dilated, although by now there is an increase in fibroblasts in this region with mild fibrosis. Only after 10 to 14 weeks of treatment do the histological appearances return to normal.
Minor changes that have been reported in psoriasis of the scalp include sebaceous gland atrophy, a decrease in hair follicle size, and thinner hair shafts. Other features of scalp psoriasis include dilatation of infundibula with parakeratosis at the lips of the infundibular ostia, papillomatosis, and scattered apoptotic keratinocytes. Munro microabscesses are said to be uncommon in this region. Another regional variation is the lessened epidermal hyperplasia in psoriasis of the penis and vulva ; spongiosis may be present.
Spongiosis has already been mentioned as a feature of the early lesions of psoriasis and of psoriasis occurring in various regions, such as the hands and feet and genital regions. It may also occur in erythrodermic psoriasis (see later). Ackerman drew attention to its presence in other situations (see p. 151 ). The author has seen several cases that caused diagnostic confusion, initially because of significant spongiosis, but that, over time, evolved into classic psoriasis. Their initial biopsies showed spongiosis, mounds of parakeratosis containing neutrophils, dilated vessels in the papillary dermis, and a mild, superficial perivascular infiltrate of lymphocytes. The term spongiotic psoriasis is an appropriate designation for these cases ( Fig. 5.6 ).
In early stages, nail plate psoriasis shows an incompletely keratinized nail plate with subungual parakeratotic scale. Imaging or rheumatology referral is advised in those with isolated nail psoriasis to evaluate for early arthritic changes, in view of the association of nail psoriasis with psoriatic arthritis. The nail plate also shows hyperkeratosis and variable neutrophil exocytosis into the parakeratotic layer. Spongiosis is a common feature of nail psoriasis. Clinically dystrophic nails show increased numbers of corneocyte layers, serous lakes, blood collections, onychokaryosis, and hypereosinophilic nuclear shadows in addition to neutrophils, but these changes can also be identified, to some degree, in clinically normal nails of patients with psoriasis. Examination of periodic acid–Schiff (PAS)–stained sections is necessary before making a diagnosis of nail psoriasis because onychomycosis and psoriasis may show similar histology ; however, it should be recognized that fungal spores or bacteria can be present in nail psoriasis.
In erythrodermic psoriasis , the appearances may resemble those described in early lesions of psoriasis, possibly a reflection of the early medical intervention that usually occurs in this condition. Dilatation of superficial vessels is usually quite prominent. A cornified layer is usually absent. Sometimes the histological changes do not resemble those of psoriasis at all.
In follicular psoriasis , there is follicular plugging with marked parakeratosis in the mid-zone of the ostium. The dermal inflammatory infiltrate is both perivascular and perifollicular.
In annular verrucous psoriasis , there is exaggerated papillomatosis resulting in finger-like projections of the epidermis. Similar changes have been reported in cases called “verrucous psoriasis.” The papillomatosis and bowing of the peripheral rete ridges toward the center of the lesion mimic the appearances of verruca vulgaris.
Skin tumors have developed at sites treated with PUVA therapy, particularly after prolonged exposure. Prolonged UV-B therapy results in the accumulation of DNA photoproducts in the cells, although adaptive responses occur. The use of coal tar does not produce any appreciable increase in skin cancers. Variants of seborrheic keratosis have also been reported in psoriatic patients receiving treatment with ultraviolet radiation. Of relevance is the controversy regarding whether patients with psoriasis have an inherently low risk of developing skin cancer, although recent studies suggest that this is not so. Psoriasis may protect against the development of actinic keratoses. Another rare complication of treatment is cutaneous ulceration, which has been reported after methotrexate therapy.
With dermoscopy, psoriasis lesions show uniformly distributed dotted or pinpoint red capillaries over a light red background associated with diffuse white scales. There is congruence among the various studies in terms of the most common dermoscopic findings in psoriasis. With reflectance confocal microscopy of plaque psoriasis, hyperkeratosis presents as bright structures with detached keratinocytes, parakeratosis as refractile polygonal structures in the stratum corneum, and spongiosis as darker areas contrasting with a bright honeycombed structure, associated with round to polygonal, refractive inflammatory cells. Munro microabscesses appear as dark, roundish, well outlined areas within the epidermal layer, and dilated vessels present as round or linear dark canalicular structures at the papillary dermal level. There are significant correlations between histopathology and Doppler sonography in the diagnosis of psoriasis and the evaluation of treatment responses.
The histopathological differentiation of psoriasis from chronic eczematous dermatitis , particularly seborrheic dermatitis, is sometimes difficult. Mounds of parakeratosis with neutrophils, spongiform pustules, and clubbed and evenly elongated rete ridges are more common in psoriasis, whereas follicular plugging, shouldered parakeratosis, and prominent lymphocyte exocytosis are significantly more common in seborrheic dermatitis. Higher numbers of mitotic figures are also seen in psoriasis; on the other hand, there are no significant immunohistochemical differences between the two conditions when staining for Ki-67, keratin 10, caspase-5, and GLUT-1. Spongiotic psoriasis (discussed previously) can be very difficult to distinguish from other spongiotic processes. The presence of mounds of parakeratosis containing neutrophils and a dermal infiltrate that is usually mild are sometimes clues to the diagnosis of psoriasis. However, these distinguishing features may not be apparent in palmoplantar lesions. A study comparing palmoplantar psoriasis and hyperkeratotic palmoplantar dermatitis has shown that confluent parakeratosis, suprapapillary thinning, and dermal edema were more commonly observed in palmoplantar psoriasis, whereas an inflammatory infiltrate confined to the papillary dermis was a significant feature in palmoplantar dermatitis. These lesions could not be differentiated by such changes as the presence of neutrophils, fibrin globules in the stratum corneum, or spongiosis. As a further complication, there may be overlapping features in psoriatic patients who also develop allergic contact dermatitis—so-called eczema in psoriatico —and the latter lesions also have immunohistochemical features that overlap with both conditions. One difference is a significantly higher number of dermal CD8 + T cells in eczema in psoriatico than in either allergic contact dermatitis or psoriasis.
Differentiation of late lesions of psoriasis from lichen simplex chronicus may be difficult, although in the latter condition the suprapapillary plates and granular layer are usually more prominent and there may be vertically oriented collagen bundles in the papillary dermis. Spongiosis is sometimes present in the rete ridges in lichen simplex chronicus if it is superimposed on an eczematous process. Psoriatic neurodermatitis needs consideration (discussed previously).
Well-developed spongiform pustulation is a feature that favors psoriasis and a limited number of other conditions: Reiter's syndrome, geographic tongue, candidiasis, and sometimes necrolytic migratory erythema. Other conditions that show psoriasiform acanthosis, such as digitate dermatosis and pityriasis rubra pilaris , lack neutrophilic aggregates and usually fail to show the degree of acanthosis seen in fully developed plaque lesions of psoriasis. In pityriasis rubra pilaris , there is mild to moderate psoriasiform hyperplasia, parakeratotic lipping of follicles, and, in some lesions, alternating zones of orthokeratosis and parakeratosis in both horizontal and vertical directions.
Pustular psoriasis has more prominent spongiform pustulation than psoriasis vulgaris, particularly at the shoulders of the lesions.
Pellagra lesions have microscopic features that are similar to psoriasis (see later). Prominent pallor of superficial keratinocytes is usually a distinctive feature, but as noted earlier, some pallor in this zone can also be observed in psoriasis. In a recently reported case, a patient whose psoriasis was minimally responsive to therapy underwent a nutritional evaluation and was found to be niacin deficient, associated with excessive alcohol intake. In this case, severe pellagra complicated psoriasis, though a biopsy evaluation showed only subtle epidermal pallor. Marked improvement followed niacin supplementation combined with antipsoriatic therapies. The importance of histopathological verification of psoriasis before the initiation of systemic therapies was emphasized in a recent case in which cutaneous lesions believed to be atypical psoriasis became worse on TNF-α inhibitor therapy; eventually, a biopsy (and other studies) demonstrated a transformed cutaneous T-cell lymphoma.
Dermoscopy may be useful in differential diagnostic situations where psoriasis is a consideration. Features of scalp psoriasis, including dotted or glomerular vessels, red loops, hairpin vessels, white scales, and punctate hemorrhages, differ from those in seborrheic dermatitis, which include arborizing vessels, atypical red vessels, featureless areas, and honeycomb pigment. Eczematous dermatoses show yellow scales and dotted vessels in a patchy arrangement over a dull red background. In the differential diagnosis of palmar psoriasis and chronic hand eczema, the former shows diffuse white scales, whereas the latter reveals yellowish scales, brownish-orange dots/globules, and yellowish-orange crusts.
There are numerous cytoplasmic organelles in the keratinocytes, reflecting their hyperactivity. These are decreased with treatment. Tonofilaments and desmosomes are reduced in number and size, and there is also a reduction in the number of keratohyaline granules. Vessels in the papillary dermis are dilated with abundant fenestrations. Neutrophils are said to be polar in shape with ruffled cell membranes.
Psoriasiform keratosis is the name given by Walsh, Hurt, and Santa Cruz to lesions that closely mimic psoriasis in the same way that the term lichenoid keratosis is used for solitary lesions with a resemblance to lichen planus. Psoriasiform keratoses are usually solitary lesions on the extremities of elderly persons who have no other clinical features of psoriasis at the time of presentation or on subsequent follow-up examination. Other sites of involvement have been the scalp, neck, shoulders, and back. Clinically, the lesions resemble a seborrheic keratosis, basal cell carcinoma, actinic keratosis, or Bowen's disease. A diagnosis of psoriasis is only occasionally made.
The lesions are usually well-defined, scaly plaques that vary in size from 0.5 to 3 cm in diameter.
The microscopic features resemble psoriasis but with more parakeratosis and less psoriasiform hyperplasia (for the amount of parakeratosis) than is usual in most cases of chronic psoriasis ( Fig. 5.7 ). This imparts a vague resemblance to a seborrheic keratosis. The parakeratosis is often diffuse, but it may be focal. There are intracorneal collections of neutrophils, often arranged in vertical tiers. There may be mild spongiosis.
The dermis shows a mild to moderate superficial perivascular infiltrate of lymphocytes. Some vascular proliferation is often present, but this may reflect the anatomical site (lower legs) of many lesions. Human papillomavirus type 6 was detected in one lesion using polymerase chain reaction technology.
A PAS stain is negative for fungal organisms.
Psoriasis, seborrheic dermatitis, and cases with overlap features may occur in patients infected with HIV. The term AIDS-associated psoriasiform dermatitis has been used, particularly for those cases with features of both conditions. Interestingly, there is often more uniformity in the histopathological expression than in the clinical presentations. In some circumstances, onset of the disease, or its exacerbation, has been associated with the initial seroconversion. In others, exacerbations are associated with cutaneous or systemic infections. The severity of the disease is variable. A Reiter's syndrome–like pattern has been seen in this condition. There are differences in epidermal expression of heat shock proteins HSP65 and HSP72 in AIDS-associated psoriasiform dermatitis compared with that in psoriasis, seborrheic dermatitis, and normal skin in non–HIV-infected patients. These differences include intensity (less intense expression in AIDS-associated psoriasiform dermatitis) and distribution and cellular pattern of expression. The authors postulate that the differences could be explained by altered interaction of T cells and keratinocytes in states of immune dysregulation such as AIDS.
The epidermis shows psoriasiform hyperplasia, but unlike psoriasis, there is no thinning of the suprapapillary plate. There are scattered apoptotic keratinocytes within the epidermis, usually associated with some lymphocyte exocytosis. Perivascular lymphocytes in the dermis may show karyorrhexis, giving rise to small amounts of nuclear dust. Plasma cells are often present in small numbers.