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Review

The histopathological landscape of the major psoriasiform dermatoses

Raluca Balan1, Adriana Grigoraș*,1, Diana Popovici2, Cornelia Amălinei1

1 Department of Morphofunctional Sciences I - Histology, "Grigore T. Popa" University of Medicine and Pharmacy, Iasi, Romania, 2 Department – Medicine of Mother and Child, "Grigore T. Popa" University of Medicine and Pharmacy, Iaşi, Romania

Abstract Psoriasiform dermatoses represent a wide spectrum of inflammatory conditions, with several major forms represented by , as the prototype of this category, followed by pustular psoriasis, Reiter’s syndrome, rubra pilaris, and large-plaques . They create a diagnostic challenge, both clinical and histopathological, because of their complexity and frequent overlapping of the microscopical features. The characteristic histopathological features of psoriasiform reaction comprise extensive hyperkeratosis, with horizontally confluent but vertically intermittent parakeratosis, which alternate with orthokeratosis, thin granular layer, with relative frequent mitoses, uniform elongated and fused rete ridges, edematous superficial papillary dermis, with dilated capillaries, perivascular lymphocytic infiltrate, Munro’s microabscesses, and spongiform pustules of Kogoj. Our paper aims to review the histopathology of major form of psoriasiform dermatoses and to emphasize the characteristic microscopical differences between them, for a better approach of the diagnosis as an important key for clinical and therapeutical management. Using the clinicopathological correlations, a thoroughly evaluation of the microscopical features and compartments distribution or special stainings and techniques, the range of differential diagnosis can be decreased and a more accurate diagnostic can be usually achieved. The insights into the pathogenic mechanisms can lead to new therapeutic opportunities targeted to the specific type of inflammatory lesion.

Keywords: psoriasis; immune-mediated dermatitis; keratinocyte proliferation; differential diagnosis

Introduction histological mark being regular elongation of rete ridges, due to greater keratinocyte Inflammatory dermatoses comprise a large proliferation, partially or totally involving the spectrum of clinico-morphological entities, the [1]. Although the general histological most common, known as major forms of features are shared by most of the psoriasiform dermatoses, being: psoriasis, inflammatory dermatoses, there are specific pustular psoriasis, Reiter’s syndrome, microscopical aspects which are , lichen simplex pathognomonic for each major form of this chronicus, and large-plaque parapsoriasis disease, which highlight the differences (parapsoriasis en grandes plaques). Psoriasis between all inflammatory dermatoses in terms represents the prototype of this category, of clinical appearance, pathogenesis and which can be defined according to histopathological characteristics related to the inflammation and epidermal changes, the quality of scales and the distribution and composition of the inflammatory infiltrate [1]. The aim of our study is to review the main Received: June 2019; Accepted after review: pathogenetic mechanisms and the clinico- September 2019; Published: September 2019. *Corresponding author: Adriana Grigoras, histopathological diagnostic features of major "Grigore T. Popa" University of Medicine and form of psoriasiform dermatoses and to Pharmacy, Iași, 16 Universitatii Street, Iasi, Romania. emphasize the characteristic microscopical Email: [email protected] differences between them, for a better

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approach of the diagnosis, as an important key neutrophils, T lymphocytes, and macrophages for clinical and therapeutic management. [3, 6]. The abnormal skin activity is managed by various proteins with different cellular activities, which are associated with the Pathogenesis pathogenesis of the diseases, such as: signal transducer and activator of transcription Psoriasis is considered a multifactorial (STAT), S100 proteins, Wnt family membrane immune-mediated dermatitis, with a complex 5a (Wnt5a) protein, p53/TP53 or tumor and controversial pathogenesis [2], including protein, enzyme biomarkers, retinoic acid an autoimmune component, with a variable related orphan nuclear receptor gamma geographical and ethnical incidence. The (RORγ/RORγt), tumor necrosis factor (TNF)- pathogenetic mechanisms are under the like weak inducer of apoptosis (TWEAK), regulation of the keratinocytes, immune cells, aquaporin-3 (AQP3), galectin-3, and the and different cytokines, some of their changes soluble form of β-amyloid precursor protein being considered epiphenomena or later (sAPPα) [7]. The earliest vascular changes events [3]. observed in psoriasis facilitate the traffic of The most frequent forms (psoriasis, Th1 lymphocytes subclass in the skin, pustular psoriasis, Reiter’s syndrome) share preserving the psoriatic plaque [3]. common immune-mediated mechanisms, Some subpopulations of T regulatory cells which involve certain human lymphocyte (Tregs), like CD4+CD25high T cell and IL-35, antigens - HLA-B13, HLA-Bw17, HLA-B27, the as well as semaphorin3A and neuropilin-1 latter being known as a major factor for the expressing Tregs, which help to preserve the pathogenesis of ankylosing spondylitis, a skin immune tolerance to commensal chronic immune-mediated inflammatory microbes, are significantly decreased in disease with systemic involvement [4] and for psoriasis [3, 8]. Reiter’s syndrome genetic component, where In this regard, it was admitted that the the reactive disease is triggered by enteric mechanism of the psoriasis can be also infections, such as Chlamydia subspecies [1, related to a dramatic decrease of 3]. The association of psoriasis and arthritis is immunotolerance to cutaneous also described in children, as juvenile psoriatic microorganisms. In this respect, a possible arthritis (JPsA), a rare disease in which relationship between psoriasis as well as patients can develop besides the above plaque psoriasis with Crohn disease, conditions, plantar fasciitis [5]. The genetic periodontitis, and Streptococcus pyogenes it mechanisms in psoriasis are supported by the was found, conditions related to abnormal „allelic instability in mitosis” model [1]. immune tolerance to intestinal and oral Lichen simplex chronicus (LSC) is related microenvironment [9]. to mechanical stimuli which are responsible for A recent study demonstrated the impact of the specific pruritus, with secondary microRNA-187 (miR-187, the most dynamic lichenification, completed by a psychogenic form of the small noncoding RNA molecules) component [1]. on cellular functions, showing that its For the parapsoriasis spectrum of downregulation in psoriatic lesions and diseases, both the relationship between large- cytokines-triggered keratinocytes inhibits the plaque parapsoriasis and cells hyperproliferation through CD276, while and the possibility for parapsoriasis to be part themiR-187’s overexpression decreases of cutaneous T-cell lymphoma are related to acanthosis, which led to psoriasis outcome abnormalities of T-cell proliferation and improvement in mouse models [10]. In another antigen expression [1]. study, which used quantitative polymerase The considered inflammatory dermatoses chain reaction (qPCR), it was emphasized that are characterized by hyperproliferative miR-126 is positively correlated with psoriasis epidermis due to keratinocytes hyperactivation severity index score, its upregulation and intense inflammatory dermic activity, promoting proliferation and keratinocytes' especially supported by dendritic cells,

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inflammation by suppressing cell apoptosis Pustular psoriasis can be associated [11]. with typical plaque-type lesions, as sterile Another mechanism which is considered pustules on palms and soles or can be to have a major role in the psoriasis generalized with systemic symptoms, as pathogenesis and its related inflammatory skin confluent sterile pustules over the trunk and dermatoses is the IL-1β-IL-1R signaling extremities [1]. Localized psoriasis includes pathway which may be involved in the several clinical forms generically known as amplification of the skin inflammatory cascade palmoplantar psoriasis, like: pustular psoriasis through the regulation of dermal IL-17- of Barber, of Andrews, producing cells and stimulation of acrodermatitis of Hallopeau [1], which share keratinocytes [12, 13]. However, plaque and similar histopathological features. The show important differences generalized von Zumbusch episodic psoriasis between the phenotype and function of T can be associated with hypocalcemia and may lymphocytes, IFN-γ and IL-17 from CD4+T be accelerated by systemic corticosteroids, cells being involved in guttate psoriasis, while iodides, salicylates, and progesterone [16, 17]. IFN-γ and IL-17 from CD8+T cells are During pregnancy, pustular psoriasis is essential in the pathogenesis of plaque manifested as herpetiformis, with a psoriasis [3, 14, 15]. generalized distribution of the lesions [1]. The disease can also evolve with arthritis, Clinical forms and patterns , or mucous membrane lesions such as fissured and geographical tongue [3]. One of the most important clinical aspects Several variants of pustular psoriasis were of psoriasis is represented by the evolution as described, as following: acral variant, chronic relapsing episodes of remission and developed on a background of acrodermatitis exacerbation. The most characteristic form of continua, exanthematic form, diaper pustular psoriasis is psoriasis vulgaris, presented as psoriasis, annular psoriasis, linear psoriasis, well delimitated individual erythematous and localized variant [3]. lesions, with a thick and silvery scale, Reiter’s syndrome tend to affect young sometimes diagnosed by Auspitz sign, in men, being highlighted by the specific triad of which forced elimination of scales leads to urethritis (with negative urethral cultures), minimal areas of bleeding [1]. Psoriasis arthritis, and conjunctivitis, which is complete vulgaris has a tropism for extensors, due to only in one-third of patients. Specific lesions Koebner (isomorphic) phenomenon (trauma comprise mucocutaneous forms as related lesions), while keratoderma blenorrhagicum (psoriasiform involves the flexures, presenting shiny eruption of the palms and soles), balanitis and minor scales [1]. The circinata (penile eruption), geographic tongue involvement of the leads to thickening and (ulcerative or erosive oral lesions), and yellow-brown discoloration of the nail plate, subungual pustules with oncholysis [1]. known as onychodystrophy. This lesion is Moreover, it has been associated with different rarely located in the mucosa, especially on the gut and genital infectious agents, like: Shigella glans penis, this localization being related to flexneri, Yersinia enterocolitica, uncircumcision [1]. Another form is guttate Campylobacter jejuni, Chlamydia trachomatis, (small) psoriasis, as an acute variant mainly in Ureaplasma urealyticum, and Mycoplasma [3]. children, manifested by erupted lesions on Pityriasis Rubra Pilaris (PRP) is a rare proximal extremities and trunk, as an immune- chronic papulosquamous disease, with a mediated reaction between streptococcal M seborrheic dermatitis-like onset, which evolve protein and human cutaneous tissues [1]. toward progressively confluent truncal Erythrodermic psoriasis is manifested as acuminate follicular and perifollicular generalized erythema, with important scale erythema, associated with areas of uninvolved shedding and skin vascular dilatation skin [1]. Other associations involve alopecia, preventing thermoregulation [1]. nail modifications, and rarely , different cutaneous malignancies or

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hypothyroidism [3]. While adult forms can on the age of the lesions [1, 21]. Moreover, it undergo spontaneous remission, the children is essential to take in consideration the clinical tend to have chronic disease. In addition, mimickers of the inflammatory dermatoses and human immunodeficiency virus (HIV) positive to histologically diagnose the lesion before the patients who develop PRP have systemic therapy because it can affect the conglobata or hidradenitis suppurativa [18]. specific microscopical landscape of the given Lichen Simplex Chronicus (LSC) condition [22]. (circumscribed neurodermatitis) is related to In this regard, there are used hematoxylin- repetitive mechanical trauma and presents as eosin (H&E) staining, as well as acid periodic- well-defined papules or plaques, frequently Schiff reactive (PAS) staining, for the hyperpigmented and always associated with assessment of the basement membrane and pruritus, involving mostly the lower lateral legs, the presence of fungal organisms. Other posterior neck, and flexural areas. A specific special stainings are sometimes necessary for pattern is represented by prurigo nodularis, the diagnosis of inflammatory dermatoses, characterized by multiple and symmetrical such as: fibrin staining (Martius-Scarlet blue), lesions with dyspigmentation and scarring [1, acid mucin staining (colloidal iron Hale’s), iron 3]. It was described an oral variant, benign staining (Prussian blue), mast cells staining alveolar ridge keratosis, characterized by (toluidine blue), melanin staining (Fontana white plaques on the maxillary keratinized Masson), elastin staining (Orcein), gingiva, due to traumatic factors [3]. demonstration of calcium deposits (Von Kossa Large-plaques parapsoriasis is defined staining), amyloid staining (Congo red). by Brocq as a group of unrelated idiopathic Bacteria and fungi can also be evidentiated and asymptomatic diseases of the middle age, with Gram and Gomori stainings [21]. with a chronic evolution, which comprises Immunohistochemistry and electron large-plaque (atrophic, retiform, and microscopy have a limited value in diagnosis patchstage mycosis fungoides) and small- of inflammatory psoriasiform dermatoses plaque parapsoriasis (chronic superficial (unless they are important for differential dermatitis, digitate dermatosis), and pityriasis diagnostic with other related conditions), while lichenoides [1], also considered by others as a immunofluorescence is specific for vesiculo- component of T-cell lymphoma or mycosis bullous diseases [21]. fungoides [3, 19]. The disease presents as The characteristic histopathological irregular asymmetrical large erythematous features of psoriasis reflect its intermittent patches and plaques, which involve especially character, as follows: extensive hyperkeratosis the buttocks, flexures, and breasts, usually (Figure 1) with horizontally confluent but being unresponsive to specific treatment [20]. vertically intermittent parakeratosis, which alternate with orthokeratosis of basket-weave Histopathological features type, thin granular layer, with relative frequent mitoses, delicate psoriasiform acanthosis, and Because the skin immune response has uniform elongated and fused rete ridges limited variants of expression, the (Figure 2). The superficial papillary dermis is histopathological diagnosis of cutaneous edematous, with dilated capillaries, acting inflammatory lesions, including the upon the above neutrophilic impregnated inflammatory psoriasiform dermatoses, is granular and spinous layers, which become sometimes difficult to achieve, because of their thinner, together forming the Auspitz sign limited and common landscape [21]. The (Figure 2). About 75% of the cases present difficulty is also related to the biopsy type, pyknotic neutrophils in the stratum corneum, superficial, with less skin compartments, or as Munro’s microabscesses, and few form profound, which involves more or all skin spongiform pustules of Kogoj (aggregated compartments, for a complete and rigorous neutrophils in the stratum spinosum). The microscopical picture. The clinicopathological underlesional superficial dermis presents a correlations are also important, as both the perivascular lymphocytic infiltrate (Figure 3), histopathological and clinical aspects depend with T lymphocytes, Langerhans cells, and

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fewer neutrophils, which become more some of them overlapping the clinical abundant in the advanced lesions, and also subtypes, such as: (i) psoriatic characteristic CD11c-positive macrophages neurodermatitis, with pruritic and lichenified situated throughout the basement membrane plaques situated on the elbows and knees, [3]. Unfortunately, only few lesions are considered a special form of psoriasis characterized by this classic histological associated with lichen simplex chronicus, (ii) landscape. In early stage or eruptive forms, scalp psoriasis, with sebaceous gland atrophy the changes are nonspecific and located and smaller hair follicles, (iii) nail psoriasis, mainly in dermis, with superficial perivascular with hyperkeratosis and spongiosis, (iv) lymphocytic infiltrate, papillary edema, dilated erythrodermic psoriasis, with histological capillaries, and extravasated erythrocytes features similar with those seen in incipient (Figure 4), with associated mounded and focal psoriasis lesions, (v) follicular psoriasis, with parakeratosis and neutrophilic migration in the parakeratosis follicular plugging and overlying almost normal epidermis. The perivascular and perifollicular dermal neutrophilic infiltrate is more abundant in inflammatory infiltrate, and (vi) annular eruptive forms than in psoriasis vulgaris (Table verrucous psoriasis with exaggerated 1) [1, 3]. papillomatosis [3]. There are also described several particular histopathological variants and localizations,

Fig. 1. Psoriasis with extensive hyperkeratosis with Fig. 2. Psoriasiform reaction consistent with Auspitz horizontally confluent parakeratosis (HE, x50) sign, with epidermal hyperplasia, parakeratosis, hypogranulosis, elongated and fused rete ridges, edematous papillary dermis, with dilated capillaries (HE, x200)

Fig. 3. Perivascular lymphocytic infiltrate in the Fig. 4. Early stage psoriasis with superficial superficial dermis in psoriasis (HE, x100) perivascular lymphocytic infiltrate, papillary edema, dilated capillaries, and extravasated erythrocytes (HE, x200)

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Pustular psoriasis is microscopically lesions as mild irregular acanthosis, manifested as characteristic spongiform mounding/elevated parakeratosis, focal pustule of Kogoj, due to neutrophils migrations vacuolar changes, doubled by superficial from superficial dermal capillaries to dermis features manifested as fibrosis, and intercellular spaces of the edematous superficial perivascular lymphocytic infiltrate, Malpighian layer, leading to keratinocytes characteristic for early stages. In chronic degeneration and formation of unilocular lesions, the picture is completed by band-like pustules. The neutrophils finally arrive in the dense inflammatory infiltrate, with papillary stratum cornosum, forming Munro’s dermal fibrosis (Table 1) [1, 3]. microabscesses. The characteristic histological landscape is completed by diffuse Differential diagnosis parakeratosis, hypogranulosis, regular elongated rete ridges, as well as superficial There are various conditions which share dermis edema, with capillary dilatation and the main histopathological landscape with mixed lympho-neutrophilic perivascular psoriasis and related major psoriasiform infiltrate, aspects characteristic for psoriasis dermatoses, which are presented below vulgaris and less developed in eruptive lesions (Table 1) [1, 3, 23]. [1]. The palmoplantar pustular psoriasis of Psoriasis shares similarities with: (a) Barber and acrodermatitis continua of other diseases with epidermal neutrophilic Hallopeau are histologically manifested as microabscesses and pustules (especially in large and unilocular pustules, with spongiform the stratum corneum), like: superficial pattern (Table 1) [3]. (dermatophytosis or ) or deep The histopathological aspects of the fungal infections (PAS stain with diastase Reiter’s syndrome clinical triad are almost predigestion), impetigo (includes secondary similar with those met in pustular psoriasis: infections), (direct extensive hyperkeratosis and parakeratosis, immunofluorescence reveals IgG, IgM or thin granular layer, elongated rete ridges, and complement in the superficial vessels), Munro’s microabscesses (Table 1) [1, 3]. of infancy (subcorneal Pityriasis rubra pilaris is characterized neutrophilic pustule and perivascular by horizontal and vertical alternating areas of neutrophils and lymphocytes); (b) other ortho- and parakeratosis, with particular papulosquamous diseases with psoriasiform shoulder parakeratosis (follicular ostia acanthosis, which present as sharp parakeratotic mounds), follicular plugging, demarcated lesions, with erythema and thick irregularly elongated rete ridges, epidermal scale, regular acanthosis, clubbed rete ridges, hyperplasia and hypergranulosis, with confluent parakeratosis, like: basal cell infrequent acantholysis, and superficial carcinoma, superficial type secondary perivascular lymphocytic infiltrate (Table 1) [1, (presents also a deeper plasma cell infiltrate in 3]. the dermis), mycosis fungoides, In lichen simplex chronicus the sebaceus, irritated seborrheic keratosis, histopathologic landscape is highlighted by pityriasis rubra pilaris (usually short epithelial thickening of epidermis and papillary dermis, ridges, parakeratosis alternating with characterized by hyperkeratosis, orthokeratosis, preserved granular layer, hypergranulosis or acanthosis, irregularly without neutrophilic inflammatory infiltrate), elongated rete ridges, and fibroplasia, with Reiter’s syndrome (neutrophils in mounds), stellate or multinucleated fibroblasts, chronic eczema (irregular acanthosis), completed by perivascular lymphocytic Bowen’s disease (atypia), nummular or inflammation. In the acute form, there is an (marked spongiosis within epidermal spongiosis, without vesicles (Table rete ridges); (c) lichen simplex chronicus 1) [1, 3]. (irregular acanthosis, papillary dermal fibrosis In parapsoriasis en plaques the in vertical streaks, fewer neutrophils in stratum histopathologic aspects include epidermal corneum).

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Table 1. Clinical and histopathological aspects of the major psoriasiform dermatoses

Clinical diagnosis Differential diagnosis Histopathological Type Localization Clinical aspects Other dermatoses Special diagnosis stainings/ techniques Extensive hyperkeratosis with confluent Chronic spongiotic parakeratosis

dermatitis PAS stain with Scalp Sharply circumscribed Uniform elongated and Superficial cutaneous diastase Groin plaque with silvery fused rete ridges fungal infections predigestion Extensors scale Papillary dermal edema Secondary syphilis Gram and surfaces Auspitz sign Dilated tortuous Reiter’s syndrome Gomori Psoriasis Nails Koebner phenomenon capillaries Lichen simplex stainings Munro’s microabscesses chronicus Spongiform pustule of Kogoj Localized palmoplantar psoriasis (Barber) Acrodermatitis continua of Hallopeau Pustular bacterid of Spongiform pustule of Andrews Dyshidrotic aczema Kogoj PAS stain with Typical plaque-like Pustular Munro’s microabscesses diastase Palms and soles lesions Superficial fungal Diffuse parakeratosis predigestion Trunk von Zumbusch infection Hypogranulosis Gram and Extremities episodic psoriasis Subcorneal pustular Elongated rete ridges Gomori Confluent sterile dermatosis of Superficial dermis edema stainings pustules Sneddon-Wilkinson Dilated capillaries

Pustularpsoriasis Underlying erythema Oral lesions Precipitated by medications (pregnancy) Hyperkeratosis with

confluent parakeratosis Uniform elongated rete ridges Triad: Papillary dermal edema Psoriasis Palms and soles Urethritis Dilated tortuous Chronic spongiotic - Penile lesions Arthritis capillaries dermatitis Conjunctivitis Munro’s microabscesses Secondary syphilis Spongiform pustule of Kogoj Reiter’ssyndrome Superficial perivascular lymphocytic infiltrate Vertical and orizontal orthokeratosis and parakeratosis Psoriasis Acuminate follicular Shoulder parakeratosis Chronic dermatitis Scalp papules Follicular plugging Trunk Erythroderma - Irregularly rete ridges Discoid

Pilaris Palms and soles Palmoplantar Thickened suprapapillary erythematosus keratoderma plates Vitamin A deficiency

PityriasisRubra Superficial perivascular lymphocytic infiltrate

Prominent pruritus Thicker epidermis and Psoriasis Well-demarcated papillary dermis Seborrheic dermatitis PAS stain with Lower lateral legs plaques Stellate fibroblasts Chronic spongiotic diastase Posterior neck Lichenification Superficial perivascular dermatitis predigestion

Flexures lymphocytic infiltrate Lichen

Simplex Superficial cutaneous Gram and

Chronicus Excoriation Epidermal spongiosis fungal infections Gomori (acute form)

stainings

Mild irregular achantosis Scaly erythematous Mounding parakeratosis Buttocks Guttate psoriasis

patches and plaques Papillary dermal fibrosis plaque

- Flexures Mild chronic dermatitis - unresponsive to Focal vacuolar change Breasts Mycosis fungoides treatment Superficial perivascular

lymphocytic infiltrate

Large Parapsoriasis

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Pustular psoriasis is more related to the dermis), mycosis fungoides, nevus dyshidrotic eczema (more spongiotic, with sebaceus, irritated seborrheic keratosis, intraepidermal pustules and eosinophilic pityriasis rubra pilaris (usually short epithelial dermal infiltrate which can indicate also a ridges, parakeratosis alternating with pustular drug eruption), superficial fungal orthokeratosis, preserved granular layer, infections (pustules in the stratum corneum), without neutrophilic inflammatory infiltrate), subcorneal pustular dermatosis of Sneddon- Reiter’s syndrome (neutrophils in mounds), Wilkinson (subcorneal pustules, less chronic eczema (irregular acanthosis), parakeratosis and epidermal hyperplasia). Bowen’s disease (atypia), nummular or Because Reiter’s syndrome and pustular contact dermatitis (marked spongiosis within psoriasis share the same histological features, rete ridges); (c) lichen simplex chronicus clinical correlations are mandatory. However, (irregular acanthosis, papillary dermal fibrosis in Reiter’s syndrome there is more prominent in vertical streaks, fewer neutrophils in stratum hyperkeratosis and a significant perivascular corneum). inflammatory infiltrate. Pustular psoriasis is more related to For Pityriasis Rubra Pilaris, where the dyshidrotic eczema (more spongiotic, with clinical aspects are primordial, the differential intraepidermal pustules and eosinophilic diagnostic comprises: (a) other dermal infiltrate which can indicate also a papulosquamous diseases (mainly psoriasis), pustular drug eruption), superficial fungal (b) other conditions with follicular plugging infections (pustules in the stratum corneum), (discoid lupus erythematosus with lichenoid subcorneal pustular dermatosis of Sneddon- inflammation, , seborrheic Wilkinson (subcorneal pustules, less dermatitis, lichen simplex chronicus, parakeratosis and epidermal hyperplasia). vulgaris, keratosis pilaris, lesions of vitamin A Because Reiter’s syndrome and pustular deficiency, both with less epidermal psoriasis share the same histological features, hyperplasia), or (c) other diseases with clinical correlations are mandatory. However, psoriasiform epidermal hyperplasia (Bowen’s in Reiter’s syndrome there is more prominent disease, chronic eczema, clear cell hyperkeratosis and a significant perivascular acanthoma, mycosis fungoides which presents inflammatory infiltrate. atypical epidermotropism, Reiter’s syndrome For Pityriasis Rubra Pilaris, where the (dilated and tortuous capillaries, neutrophils in clinical aspects are primordial, the differential mounds). diagnostic comprises: (a) other Psoriasis shares similarities with: (a) papulosquamous diseases (mainly psoriasis), other diseases with epidermal neutrophilic (b) other conditions with follicular plugging microabscesses and pustules (especially in (discoid lupus erythematosus with lichenoid the stratum corneum), like: superficial inflammation, atopic dermatitis, seborrheic (dermatophytosis or candidiasis) or deep dermatitis, lichen simplex chronicus, ichthyosis fungal infections (PAS stain with diastase vulgaris, keratosis pilaris, lesions of vitamin A predigestion), impetigo (includes secondary deficiency, both with less epidermal infections), vasculitis (direct hyperplasia), or (c) other diseases with immunofluorescence reveals IgG, IgM or psoriasiform epidermal hyperplasia (Bowen’s complement in the superficial vessels), disease, chronic eczema, clear cell acropustulosis of infancy (subcorneal acanthoma, mycosis fungoides which presents neutrophilic pustule and perivascular atypical epidermotropism, Reiter’s syndrome neutrophils and lymphocytes); (b) other (dilated and tortuous capillaries, neutrophils in papulosquamous diseases with psoriasiform mounds). acanthosis, which present as sharp Lichen simplex chronicus has demarcated lesions, with erythema and thick histological similarities with other significant scale, regular acanthosis, clubbed rete ridges, pruriginous conditions, other papulosquamous confluent parakeratosis, like: basal cell diseases with epidermal hyperplasia, carcinoma, superficial type secondary syphilis seborrheic dermatitis, chronic fungal infections (presents also a deeper plasma cell infiltrate in (more often with neutrophils in the stratum

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corneum), but especially with psoriasis diseases, which share most of their (confluent parakeratosis, neutrophils in histopathological features, thus representing a mounds, regular clubbed rete ridges, genetic challenge in histopathology. component). Using the clinical data, a thoroughly For parapsoriasis, the histopathological evaluation of the microscopical features and features are nonspecific, thus the clinical compartments distribution or special stainings diagnostic is essential. In early lesions of and techniques, including molecular markers parapsoriasis, the differential diagnosis identification, the range of differential comprises superficial perivascular dermatitis diagnosis can be decreased and a more or mild chronic dermatitis. Other conditions accurate diagnostic can be usually achieved. which share histological similarities with Additionally, clinicopathological parapsoriasis include: (lasts correlations may be helpful regarding the only 6 weeks), (lasts disease stage or previous therapies. months to several years, mainly in childhood Moreover, understanding the pathogenic and young adulthood, with lesions smaller mechanisms and closely monitoring the than 5 mm), mycosis fungoides (larger development of these major psoriasiform plaques, Pautrier microabscesses, pan T-cell dermatoses can lead to new therapeutic markers depletion, atypical T-cell gene opportunities targeted to the specific type of rearrangements, and significant inflammatory lesion. epidermotropism).

Conflict of interest/Funding Statement Conclusions The authors have no conflict of interest to The major psoriasiform dermatoses declare. represent complex inflammatory skin

References

1. Gillum PS, Golitz LE. Psoriasiform Dermatitis. 8. Sabag AD, Dias-Polak D, Bejar J, Sheffer H, In Barnhill, RL, Crowson, AN (Ed.). Textbook of Bergman R, Vadasz Z. Altered expression of Dermatopathology. 2nd edition. McGraw-Hill; regulatory molecules in the skin of psoriasis. 2004:61-77. Immunol Res 2018; 66(6):649-654. 2. Das RP, Jain AK, Ramesh V. Current concepts 9. Lewis DJ, Chan WH, Hinojosa T, Hsu S, in the pathogenesis of psoriasis. Indian J Feldman SR. Mechanisms of microbial Dermatol 2009; 54(1):7–12. pathogenesis and the role of the skin 3. Weedon D. The psoriasiform reaction pattern, microbiome in psoriasis: A review. Clin In Weedon’s Skin Pathology. 3rd edition. Dermatol 2019; 37(2):160-166. Churchill Livingstone; 2010:71-91. 10. Tang L, He S, Zhu Y, et al. Downregulated 4. Chen B, Li J, He C, et al. Role of HLA-B27 in miR-187 contributes to the keratinocytes the pathogenesis of ankylosing spondylitis. Mol hyperproliferation in psoriasis. J Cell Physiol Med Rep 2017; 15:1943-1951. 2019; 234(4):3661-3674. 5. Yener GO, Tekin ZE, Yuksel S. Psoriatic 11. Feng S, Wang L, Liu W, Zhong Y, Xu S. MiR- fasciitis in a pediatric patient: A case report. 126 correlates with increased disease severity World J Clin Cases 2019; 7(1): 69-72. and promotes keratinocytes proliferation and 6. Uttarkar S, Brembilla NC, Boehncke WH. inflammation while suppresses cells' apoptosis Regulatory cells in the skin: Pathophysiologic in psoriasis. J Clin Lab Anal 2018; role and potential targets for anti-inflammatory 32(9):e22588. therapies. J Allergy Clin Immunol 2019; 12. Cai Y, Xue F, Quan, C, et al. A Critical Role of 143(4):1302-1310. the IL-1β-IL-1R Signaling Pathway in Skin 7. Yadav K, Singh D, Singh MR. Protein Inflammation and Psoriasis Pathogenesis. J biomarker for psoriasis: A systematic review on Invest Dermatol 2019; 139(1):146-156. their role in the pathomechanism, diagnosis, 13. Jaiswal AK, Sadasivam M, Archer NK, et al. potential targets and treatment of psoriasis. Int Syndecan-1 Regulates Psoriasiform Dermatitis J Biol Macromol 2018; 118(Pt B):1796-1810.

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by Controlling Homeostasis of IL-17-Producing responsive to triple antiretroviral therapy. Br J γδ T Cells. J Immunol 2018; 201(6):1651-1661. Dermatol 1999; 140:931-934. 14. Yan K, Han L, Deng H, et al. The distinct role 19. Simon M, Flaig MJ, Kind P, et al. Large plaque and regulatory mechanism of IL-17 and IFN-γ parapsoriasis: Clinic and genotyping in the initiation and development of plaque vs correlations. J Cutan Pathol 2000; 27:57-60. guttate psoriasis. J Dermatol Sci 2018; 20. Lambert WC, Everett MA. The nosology of 92(1):106-113. parapsoriasis. J Am Acad Dermatol 1981; 15. Brembilla NC, Senra L, Boehncke WH. The IL- 5:373. 17 Family of Cytokines in Psoriasis: IL-17A and 21. Alsaad KO, Ghazarian D. My approach to Beyond. Front Immunol 2018; 9:1682. superficial inflammatory dermatoses. J Clin 16. Braverman JM, Cohen I, Black MM. Metabolic Pathol 2005; 58:1233–1241. and ultrastructural studies in a patient with 22. Rohl R, Bax D, Schierer S, Bogner PN, pustular psoriasis. Br J Dermatol 1972; Hernandez-Ilizaliturri F, Paragh G. A case for 105:189. histologic verification of the diagnosis of 17. Shelly WB. Generalized Pustular Psoriasis: atypical psoriasis before systemic therapy. Consultations in . Philadelphia: JAAD Case Rep 2018; 4(5):465-467. Saunders, 1972. 23. Rapini RP. Practical Dermatopathology. 2nd 18. Gonzales-Lopez A, Velasco E, Pozo T, Del Edition. Elsevier Saunders, 2012. Villar A. HIV-associated pityriasis rubra pilaris

DOI: 10.22551/2019.24.0603.10155 68 Arch Clin Cases 2019; 6(3):59-68