Histopathology of' psoriasis Histopatlwwgic spectrum oj psoriasis S. Kaddu, S. Hodl and H.P. Soyer S UM MA R Y------ -------- ---------- The many clinical faces of psoriasis are reflected by the spectrum of histopathologic changes ranging from guttate psoriasis to generalized pustular psoriasis. Psoriasis is a dynamic process and consequently the morphologic changes vary during the evolution and subsequent resolution of the individual lesions. Far example, a fully developed psoriatic lesion reveals psoriasiform acanthosis of the epidermis characterized by elongated thin or club shaped rete ridges of equal length alternating with thin dermal papillae that are covered by thin suprapapillary plates. Typically, there is confluent parakeratosis, which contains accumulation of neutrophils. The granular layer is decreased or absent. In the upper part of the dermis there is a moderately dense perivascular and interstitial infiltrate of lymphocytes in association with dilated spiraled capillaries in the dermal papillae and marked edema of the papillary dermis. Besides early, fully developed and late lesions of "classical" psoriasis, palmoplantar psoriasis, pustular psoriasis and erythrodermic psoriasis are ali characterized by distinctive morphologic changes that, in many instances, allow a histopathologic diagnosis with certainty. The most important differential diagnoses from a histopathologic point of view are as follows: psoriasiform trichophytia, pityriasis rubra pilaris, pityriasis rosea, nummular dermatitis, chronic contact dermatitis, lichen simplex chronicus and rupial syphilis. In conclusion , the histopathologic findings of the many faces of psoriasis are distinctive and allow a definitive diagnosis by the experienced dermatopathologist in nearly ali instances. Unti l today no laboratory methods including modern molecular technologies are replacing conventional histopathology in the diagnosis of psoriasis. Introduction Psoriasis vulgaris is a re latively common skin condition that affects about 1 o/o to 2% of the general population (1 ,2) . A genetic predisposition has been shown, but no clear pattern of inheritance has yet been demonstrated . Psoriasis vulgaris manifes ts itself in the second and third decades of life mainly as generali zed erythematous plaques (plaque type). The disease may also show severa! other clinical variants mainly inclucling R e view 94 acta dermatovenerologica A.P.A. Vol 8, 99, No 3 R e view An early lesion of psoriasis: Fig. 1a) There is psoriasiform hyperplasia of the epidermis with focal parakeratosis containing neutrophi/s (haematoxylin-eosin 50x). eruptive guttate, pustular, erythrodermic and geographic types (1 -4). Because of this wide spectrum of clinical features, the correct diagnosis may sometimes not be suspected clinically. Histopathology is useful in confirming the diagnosis and excluding other conditions that may mimic psoriasis. Histopathologic findings vary depen- A we/1- deve/oped lesion of plaque type psoriasis: Fig. 2a) There is prominent psoriasiform epidermal hyperplasia, hypogranu/osis and confluent parakeratosis with col/ections of neutrophils in stratum corneum (haematoxylin-eosin 50x). Histopathology oj psoriasis Fig. 1 b) Note the focal /oss of the granu/ar layer, and dilated, tortuous capillaries in the dermal papil/ae; spongiform pustule of Kogoj in the spinous layer (haematoxylin-eosin 250x). ding on the clinical type, age of the lesion, and with presence and degree of irritation or previous treatment (1 ,2,5-8). A correct diagnosis often requires a correlation between the clinical and histopathologic features . In this article, we highlight the main histopathologic findings of psoriasis in the context of the different clini- cal types. In addition, a few clues that may be helpful in making a prompt diagnosis, will be mentioned. Plaque type psoriasis Plaque type of psoriasis vulgaris presents mainly as sharply demarcated erythematous plaques with silvery scales showing predilection for extensor surfaces of the elbows and knees, presacral areas and the scalp (3,4,9) . It is further characterized by a chronic course with re- missions and exacerbations. The nails are frequently affected (pits and onycholysis) . About 15% of cases show joint involvement in the form of arthritis . The Fig. 2b) Note keratinocytes with pate cytoplasm, and a few lymphocytes in the /ower portion of the epidermis (haematoxylin-eosin 250x). acta dermatovenerologica A.P.A. Vo l 8, 99, No 3 --- - - ----------- - --- - - - - - ----- -- 9J Histopathology of psoriasis lesions may initially clinically simulate a variety of inflammatory skin conditions e.g., pityriasis rosea, secondary syphilis, pityriasis rubra pilaris, chronic nummular and dyshidrotic eczema, and lichen simplex chronicus. Histopathologic findings vary mainly with the age of the lesioqs. Early lesions Early lesions _are characterized mainly by slight epidermal hyperplasia with mounds of parakeratosis containing neutrophils, focal loss of granular layer, and slight exocytosis of inflammato1y cells with spongiosis (Figs. la and b) (1,2,5-8,10). The epidermis reveals an increased number of mitotic figures. The papilla1y dermis sometimes shows slight edema and there are dilated, tortuous capillaries in the dermal papillae. A sparse, superficial perivascular inflammatory infiltrate consisting of mononuclear cells and neutrophils, but usually without eosinophils, is present in the upper dermi.'i. The main histopathologic differential diagnoses at this stage include conditions that reveal spongiotic dermatitis w ith focal parakeratosis, e.g ., nurnmular and atopic dermatitis , pityriasis rosea, superficial gyrate erythemas, seborrheic dermatitis, and superficial fungal infections. In contrast to early psoriasis vulgaris, both nummular and atopic dermatitis exhibit more prominent acanthosis and may show scattered eosinophils w ithin the dermal infiltrate. Pityriasis rosea and superficial gyrate e1ythemas reveal mounds of parakeratosis that do not contain neutrophils. Seborrheic dermatitis dis- plays mourids of parakeratosis containing plasma loca- ted mainly at the edges of infundibular ostia. Well-developed lesions The histopathologic features of most well-developed lesions of plague type psoriasis are characteristic and include prominent psoriasiform epidermal hyperplasia, mainly involving the rete ridges and sparing the epi- dermis over the dermal papillae, hypogranulosis, and confluent parakeratosis with collections of neutrophils in stratum corneum (Fig. 2a) (1,2,5-8). Neutrophils may also be observed in the malphigian layer of the epider- mis (spongioform pustules of Kogoj) as well as dermal papillae. The u pper portions of the epidermis may reveal keratinocytes with a pale cytoplasrn (Fig. 2b). Exocytosis of lymphocytes may be observed in the lower portions of the epidermis ( 6) . The basal layer often reveals a focal increase in mitotic figures. The dermal papillae are typically thinned and elongated, and contain fibrillary 96 collagen and dilated capillaries. A perivascular infla- mmato1y infiltrate of lymphocytes , histiocytes and neu- trophils is usually present in the upper dermis. Histo- pathologic differential diagnoses mainly include sub- acute contact eczema, nummular dermatitis and psoria- sifonn fungal infections. Late lesions Late lesions of plague type psoriasis are ch a- racterized mainly by acanthosis with elongation of the rete ridges . Instead of parakeratosis, compact ortho- keratosis is usually present (Figs. 3a and b) (11). There is conspicuous bulbous enlargement of the tips of the evenly elongated rete ridges with narrowing at the bases, and sometimes "bridging" of the re te ridges. Th e suprapapillaiy plate remains thinned slightly and there are dilated tortuous capillaries in the dermal papillae. Late lesions of plague type psoriasis may histo- pathologically simulate lichen simplex chronicus. However, lichen simplex chronicus displays more prominent fibrosis of the papillary dermal collagen and marked hypergranulosis, whereas late chronic plague type of psoriasis exhibits only subtle fibroplasia in the papilla1y dermis. Treatment and irritation (rubbing and scratching) may alter slightly the histopathologic features of pso- riasis vulgaris. Pretreated psoriatic plagues often show a minimal inflammatory infiltrate , a reduction in amount of epidermal hyperplasia and a less reduced granular layer (1,5) . In some of these cases, there is also an increase of fibroblasts in the papillaiy dermis. Guttate psoriasis Eruptive guttate psoriasis commonly affects rela- tively younger individuals aged between 10 to 20 years. The skin condition is characterized by an acute outbreak of generalized, small, red, nonconfluent papules and plagues, which often accompany a streptococcal throat infection. The main clinical differential diagnoses inclu- de pityriasis rosea and lichen planus. Histopathologic findings in guttate psoriasis are similar to those in early lesions of plague type psoriasis (see above) and will not be discussed in further details. Pustular psoriasis Pustular psoriasis may develop in tl1e setting of well- established plague-type psoriasis. The skin condition is characterizecl by pustules commonly localizecl Review acta dermatovenerologica A.P.A. Vol 8, 99, No 3 R eview A late lesion of plaque type psoriasis: Fig. 3a) There is acanthosis with compact orthokeratosis (haematoxylin-eosin 50). exclusively on the palms and soles. In few patients, however, a generalized pustular form develops , often accompanied by fever and an elevated white blood celi count. Recently, Ackerman et al. have also proposed that a number of pustular skin conditions previously considered to be distinctive entities including acro- dermatitis continua of Hallopeau, dermatitis repens of Crocker, impetigo herpetiformis, keratoderma blenorr- Pustu/ar psoriasis: Fig. 4a) There is a prominent collection of neutrophils in the upper half of the epidermis (spongiform pustules of Kogoj) and spinous zone (Munro's microabscesses) (haematoxylin-eosin 50x). Histopathology of psoriasis Fig. 3b) Higher magnification shows foca/ hyper- granulosis and an inflammatory infiltrate in the upper dermis composed mainly of lymphocytes and histiocytes (haematoxylin-eosin 250x). hagicum, pustular bacterid of Andrews, subcorneal pustular dermatosis of Sneddon and Wilkinson, and geographic tongue actually represent different expre- ssions of pustular psoriasis (5) . Pustular psoriasis should clinically mainly be differentiated from superficial fungal infections. Histopathologically, pustular psoriasis generally shows similar features to those of plaque-type psoriasis except for the discrete collections of neutrophils in the spinous zone (Munro's microabscesses) , sponge-like array of neutrophils in the upper half of the epidermis (spongiform pustule of Kogoj), collections of neutro- phils beneath the cornified layer (subcorneal pustules), and/ or presence of pockets of neutrophils within the cornified layer (intracorneal pustules) (Figs. 4a and b). Pustular lesions display less marked epidermal hyperplasia when compared to plaque type psoriasis (5,12). Pustular lesions of psoriasis are histopathologically Fig. 4b) Note the sponge-/ike array of neutro- phi/s in the upper ha/f of the epidermis (spon- giform pustules of Kogoj) (haematoxylin-eosin 250x). acta dermatovenerologica A.P.A. Vol 8, 99, No 3 - ------------------------ --- --- - - 97 Histopathology of psoriasis indistinguishable from skin lesions ofReiter's syndrome. Spongiform pustules are not specific for pustular psoriasis but may also be found in a variety of other skin conclitions (e .g., dermatophytes, spirochetes) . Erythrodermic psoriasis Eiythroclermic psoriasis develops in about 2% of psoriatics usually following pustular or plaque types. In a minority of patients, erythrodermic psoriasis presents initially with no former history of the disease. Clinically, patients with erythrodermic psoriasis show extensive erythema with desquamation. These skin changes are often accompaniecl by fever, fatigue and muscle pains. The main clinical differential diagnoses include conditions that present as generalized erythro- derma (e.g., Seza1y syndrome, drng reactions). Histopathologically, erythrodermic psoriasis ge- Table 1. Clues to histopathologic diagnosis of psoriasis* Histopathologic Feature Mounds of parakeratosis with neutrophils at their summits Thin, elongated rete ridges of nearly equal length Striking pallor of cells in the upper part of the spinous layer Dilated tortuous capillaries within thinned dermal papillae ''The listing of clues was modified accorcling to Ackerman et al. (5,6). nerally shows less characteristic features (13). The subset of cases w ith more typical histopathologic changes display epidermal hyperplasia and parakeratosis con- taining neutrophils, slight exocytosis of inflammatory cells with spongiosis, and prominent dilation of the superficial bloocl vessels (Figs. 5a ancl b) (1,2 ,5). The amount of parakeratosis still adherent to the epiclermal surface is usually scant. Moreover, the strat:um corneum may be totally absent. Table 1 summarizes important clues to histopa- tho logic diagnosis of psorias is, w hich have been compiled mainly from publications by AB Ackerman et al. (5,6). 98 Erythrodermic psoriasis: Fig. 5 a) There is epidermal hyperplasia and parakeratosis containing neutrophils, slight exocytosis of inflammatory cells, and prominent dilation of the superficial blood vessels in the upper dermis (haematoxylin-eosin 50x). Fig. 5 b) Note the scant amount of parakeratosis more or less adherent to the epidermal surface (haematoxylin-eosin 1 00x). R eview acta dermatovenerologica A.P.A. Vol 8, 99, No 3 Revi e w Histopathology c,f" psoriasis :B. E F E R E N C E S l. Weedon D. Skin pathology. Churchill Livingstone, Edinburgh, London, 1997. AUTHORS' ADDRESSES 2. MaizeJC, BurgdorfWHC, Hurt MA, LeBoit PE, MetcalfJS, Smith T, Solomon AR. Cutaneous pathology. Churchill Livingstone, Philadelphia 1998. 3. Kerkof van de PCM. Psoriasis: a spectrum of expressions. Acta Dermatovenorologica APA 1998: 7: 57- 64. 4. Kerkofvan de PCM. The differential diagnosis of psoriasis. Acta Dermatovenorologica APA 1999:8:50- 8. 5. Ackerman AB, Chongchitnant N, SanchezJ, Guo, Bennin B, Reiche! M, Randall MB. Histologic diagnosis of inflammatory skin diseases: an alogarithmic method based on pattern analysis . Lea & Febiger, Philadelphia, 1997. 6. Ackerman AB, Ragaz A. The lives of lesions, chronology in dermatopathology. Masson,New York1984. 7. Cox AJ, Watson W. Histological variations in lesions of psoriasis. Arch Dermatol 1972; 106:503-6. 8. Ragaz A, Ackerman AB. Evolution, maturation, and regression oflesions of psoriasis. AmJ Dermatopathol 1979: 1: 199-214. 9. Stern RS. Epidemiology of psoriasis. Dermatol Ciin 1995: 13: 717-22. 10. Jablonska S, Chowaniec O, MaciejowskaE. Histology of psoriasis: the role of polymorphoneutrophils. In: Beutner E, editor. Autoimmunity in psoriasis. Boca Raton, Fla: CRC Press, 1982: 21-36. 11. Griffin TD, Lattanand A, VanScott EF. Clinical and histologic heterogeneity of psoriatic plaques: therapeutic relevance. Arch Dermatol 1988: 124: 216-20. 12. P1ystowsky JH, Cohen PR. Pustular and e1ythrodermic psoriasis. Dermatol Ciin 1995: 13: 757-70. 13. Abrahams I, McCathy JT, Sanders SL. 101 cases of exfoliative dermatitis . Arch Dermatol 1963: 87: 96- 101. StevenKaddu, MD, Department oj Dermatology, University ofGraz Auenbruggerplatz 8, A-8036 Graz, Austria Stefan Hodl, MD, projessor oj dermatology, same address H Peter Soyer, MD, projessor oj dermatology, same address acta dermatovenerologica A.P.A. Vol 8, 99, No 3 -------------- ---- --- ------- - - 99