Psoriasiform Hyperplasia Research Articles

Hidradenitis suppurativa/acne inversa: bilocated epithelial hyperplasia with very different sequelae

Hidradenitis suppurativa/acne inversa is a chronic, inflammatory, scarring disease in the terminal hair follicle and apocrine gland-bearing areas (skin folds). There is considerable histological evidence that perifolliculitis and follicular hyperkeratosis precede the rupture of the follicle. The timing of the epithelial hyperplasia at the infundibula of inflamed terminal follicles has not yet been clarified. To clarify the early histopathological life of lesions ('chronology') in hidradenitis suppurativa/acne inversa, focusing on the terminal follicle structure and its surrounding tissue (hyperkeratosis, hyperplasia of follicular epithelium, perifolliculitis and rupture). In total, 485 operative specimens obtained from 128 patients with diagnosed hidradenitis suppurativa/acne inversa (all surgically treated by wide excision) were examined histologically. Two to five histological preparations (total 485) per operation area (total 196) were prepared by multiple slicing. Hidradenitis suppurativa/acne inversa showed a heterogeneous histological pattern: hyperkeratosis of the terminal follicles (89%), hyperplasia of follicular epithelium (80%), pronounced perifolliculitis (68%) and follicle rupture (24%). Perifolliculitis, follicular hyperkeratosis and hyperplasia occurred prior to the rupture of the follicle. Other histological criteria were: subepidermal cellular inflammatory infiltrate (82%), epidermal psoriasiform hyperplasia (56%), pronounced acute dermal inflammation (28%), pronounced chronic dermal inflammation (49%), and involvement of apocrine glands (52%) and subcutis (31%). Infundibular hyperkeratosis, hyperplasia of the follicular epithelium and perifolliculitis are major histopathological characteristics of hidradenitis suppurativa/acne inversa. These apparently precede rupture of the follicle. In particular, hyperplasia of the follicular epithelium probably marks the beginning of sinus formation, which usually spreads horizontally. Psoriasiform hyperplasia of the interfollicular epidermis with subepidermal inflammatory infiltrate might be interpreted as an inflammation-driven process basically identical to that which is evident at the terminal follicle. However, it does not lead to harmful and progressive sequelae like those (rupture, sinus tracts) seen at the terminal follicles.

Dystrophic calcification following neonatal heel‐prick testing

A 7-year-old boy presented with a 5-year history of dystrophic calcification manifesting as solitary nodules on the plantar aspect of both heels. Microscopic examination showed hyperkeratosis and psoriasiform hyperplasia overlying an area of dystrophic calcification. Multiple heel-prick tests carried out during the neonatal period to monitor blood glucose levels are the likely causative mechanism.

Nonmutilating palmoplantar and periorificial kertoderma: a variant of Olmsted syndrome or a distinct entity?

Olmsted syndrome is a rare keratinization disorder characterized by mutilating palmoplantar and periorificial keratoderma as the two major diagnostic features. Some authors believe that atypical cases without this standard combination may not really belong to Olmsted syndrome. Herein, we describe two familial cases with congenital nonmutilating palmoplantar and periorificial keratoderma, and discuss their similarities and differences with Olmsted syndrome. The study included two sisters who presented with focal and punctate nonmutilating palmoplantar keratoderma (PPK), periorificial hyperkeratotic plaques, and widely distributed keratotic lesions. Fragile denuded areas of the skin were found in sites exposed to trauma. Fingernails showed a characteristic form of leukonychia. Histopathology of plantar keratoderma showed psoriasiform hyperplasia with marked compact hyperkeratosis, while vicinity of denuded skin revealed thin parakeratotic zone and dissolution of the granular cell layer. Immunohistochemistry demonstrated suprabasal staining pattern for acidic keratin (AE1) and uniform positivity, starting four to six layers above the basal layer, for cytokeratin 10. Electron microscopy showed defective keratinization. Cytogenetic studies revealed normal karyotype and no chromosomal breakage. Our cases share Olmsted syndrome in the early onset, and the presence of symmetrical PPK, periorificial keratoderma and keratotic lesions. However, the striking nonmutilating nature of PPK and the presence of unique features in our patients suggest a newly described keratinization disorder.

Hidradenitis suppurativa (acne inversa): early inflammatory events at terminal follicles and at interfollicular epidermis*

Hidradenitis suppurativa (acne inversa) is a chronic suppurative and scarring inflammatory disease with predilection in the apocrine gland-bearing areas. Histological investigations in the 1990s showed keratotic occlusion of the terminal follicle structure to be the initial cause. Our investigations describe and reproduce the morphology and try to figure out very early lesions of HS. A total of 262 operative specimens from 60 patients were investigated by routine histology and 11 operative specimens by immunohistochemistry: HS is dominated by a heterogeneous histological image. 82% of the surgical specimens showed mild or pronounced follicular hyperkeratosis, whereas an isotopic hyperplasia of follicular epithelium was evident in 77%. Pronounced perifolliculitis was seen in 68% and rupture of the follicle structure in 28%. Features which had not so far been described in detail were: epidermal psoriasiform hyperplasia (43%) and subepidermal interfollicular inflammatory infiltrate (78%). In all 11 specimens, immunohistochemical investigations showed a perifollicular and subepidermal inflammation of CD-3-, CD-4-, CD-68-, CD-79- and CD-8-cells, the latter with a striking selective epitheliotropism. To conclude, we could show follicular hyperkeratosis and lymphocytic perifollicular inflammation as early patterns in pathogenesis, whereas rupture of the follicle structure takes place later. Finally, it seems that there are two hot spots of inflammatory events (perifollicular and subepidermal) composed of a comparable inflammatory cell mixture. The CD-8 cell epitheliotropism (follicular and epidermal) described here and its influence in follicular hyperkeratosis, in hyperplasia of follicular epithelium and in epidermal psoriasiform hyperplasia will be of further interest, for instance, concerning early pharmacological intervention.

Necrolytic acral erythema without hepatitis C infection

Necrolytic acral erythema is a newly described entity characterized by sharply demarcated scaly plaques on the dorsum of the hands and feet. More than 30 patients have been reported since 1996, all of whom had anti-hepatitis C virus antibody. A 32-year-old Taiwanese woman had been diagnosed with and treated for systemic lupus erythematosus with lupus nephritis about 10 years earlier. Soon thereafter, she noted several well-demarcated keratotic plaques with erythematous borders on her feet, with sparing of the soles. Histopathology showed diffuse parakeratosis with a neutrophil infiltrate, hypogranulosis, pale upper keratinocytes, scattered and grouped dyskeratotic cells, psoriasiform hyperplasia and a mild lymphocytic infiltrate in the upper dermis. The diagnosis was made after three biopsies. The lesions regularly worsened just before and during menstruation, but patch and intradermal tests for progesterone and estrogen were negative. There was no evidence of either hepatitis B or hepatitis C infection. The lesions did not respond to treatment with zinc. The rash regressed spontaneously when corticosteroids were stopped and recurred when they were restarted, finally resolving completely after she was treated with high-dose pulse steroids for her lupus.

Epidermal Vascular Endothelial Growth Factor Production Is Required for Permeability Barrier Homeostasis, Dermal Angiogenesis, and the Development of Epidermal Hyperplasia: Implications for the Pathogenesis of Psoriasis

Primary abnormalities in permeability barrier function appear to underlie atopic dermatitis and epidermal trauma; a concomitant barrier dysfunction could also drive other inflammatory dermatoses, including psoriasis. Central to this outside-inside view of disease pathogenesis is the epidermal generation of cytokines/growth factors, which in turn signal downstream epidermal repair mechanisms. Yet, this cascade, if sustained, signals downstream epidermal hyperplasia and inflammation. We found here that acute barrier disruption rapidly stimulates mRNA and protein expression of epidermal vascular endothelial growth factor-A (VEGF-A) in normal hairless mice, a specific response to permeability barrier requirements because up-regulation is blocked by application of a vapor-impermeable membrane. Moreover, epidermal vegf(-/-) mice display abnormal permeability barrier homeostasis, attributable to decreased VEGF signaling of epidermal lamellar body production; a paucity of dermal capillaries with reduced vascular permeability; and neither angiogenesis nor epidermal hyperplasia in response to repeated tape stripping (a model of psoriasiform hyperplasia). These results support a central role for epidermal VEGF in the maintenance of epidermal permeability barrier homeostasis and a link between epidermal VEGF production and both dermal angiogenesis and the development of epidermal hyperplasia. Because psoriasis is commonly induced by external trauma [isomorphic (Koebner) phenomenon] and is associated with a prominent permeability barrier abnormality, excess VEGF production, prominent angiogenesis, and epidermal hyperplasia, these results could provide a potential outside-inside mechanistic basis for the development of psoriasis.

New-onset psoriasis following treatment with the interleukin-1 receptor antagonist anakinra

Conflicts of interest: none declared. Sir, Anakinra is a recombinant human form of interleukin‐1 receptor antagonist (IL‐1Ra) that blocks interleukin‐1 (IL‐1) signalling. It is administered as a daily subcutaneous injection, and is used to treat patients with rheumatoid arthritis (RA). The drug is generally well tolerated and has a good safety profile.1 The most common adverse effects are injection site reactions.2 We report a patient with RA who developed psoriasis following anakinra therapy. Recently, other biologic anticytokine drugs, such as all of the tumour necrosis factor (TNF)‐α blocking agents (etanercept, infliximab, adalimumab), have been reported to cause or exacerbate psoriasis.3 However, to our knowledge, no psoriatic lesions have been reported in patients treated with anakinra. A 75‐year‐old woman developed in 1995 a symmetrical polyarthritis involving shoulders, small joints of hands and feet, and knees. The rheumatoid factor was negative. She fulfilled the diagnostic criteria for RA.4 There was no personal or familial history of psoriasis. She had been treated with multiple disease‐modifying antirheumatic drugs, that were discontinued because of side‐effects or lack of efficacy. Despite treatment, her RA was still active and she developed typical erosions in metacarpophalangeal joints. Therefore, she was started on combined therapy with TNF‐α antagonists and methotrexate. Etanercept and infliximab were discontinued because of lack of efficacy, and adalimumab was withdrawn because of an episode of left cardiac failure. In March 2006, anakinra (100 mg daily subcutaneously) was started. In December 2006, 9 months later, she presented with typical psoriatic, scaly, erythematous plaques on the elbows (Fig. 1a). Skin biopsy from the patient’s left elbow showed psoriasiform hyperplasia, parakeratosis and a lymphocytic infiltrate in the upper dermis, consistent with psoriasis (Fig. 1b). Treatment with anakinra was discontinued, and the psoriatic lesions improved significantly with the addition of topical steroids and vitamin D.

Psoriasis: dysregulation of innate immunity

The current understanding of the function of natural killer (NK) T cells in innate immunity and their potential to control acquired specific immunity, as well as the remarkable efficacy of antitumour necrosis factor-alpha biological treatments in psoriasis, forces us to refine the current T-cell hypothesis of psoriasis pathogenesis, and to give credit to the role of innate immunity. Psoriasis might be envisioned to be a genetically determined triggered state of otherwise dormant innate immunity. This aggravated state of innate immunity is represented by the activity of NK T cells, dendritic cells, neutrophils and keratinocytes, leading to the recruitment and activation of preferentially type 1 T cells, possibly in an antigen-independent way. Keratinocytes in psoriasis then are sensitive to the effects of T-cell activation and cytokine production, interferon (IFN)-gamma, by responding with psoriasiform hyperplasia. The chronic inflammation of psoriatic lesions suggests that this might be due to a deficiency in downregulation processes (e.g. a defect in the regulatory T-cell repertoire) and/or the persistence of an unknown trigger resulting in an exaggerated innate immune response.

CD1A Rich Inflammatory Stage of Lichen Sclerosus Et Atrophicans Mimicking Mycosis Fungoides and Extramammary Paget’S Disease

We report a case of inflammatory stage vulvar lichen sclerosus et atrophicans (LSA) with histopathologic features simulating both patch stage mycosis fungoides (MF) and extramammary Paget’s disease. The patient is a 79‐year‐old woman with an erythematous plaque on her vulva. A punch biopsy was performed that revealed mild psoriasiform hyperplasia of the epidermis with spongiosis, marked interface vacuolar alteration, scattered individual necrotic keratinocytes and Civatte bodies. A band‐like mixed inflammatory infiltrate was present in the papillary/upper dermis with prominent intraepidermal lymphocytes. Some intraepidermal lymphocytes showed atypical nuclear contours simulating the cells seen in MF. The presence of numerous intraepidermal epithelioid cells with a pagetoid distribution raised the possibility of extramammary Paget’s disease. A panel of immunohistochemical (IHC) stains showed a reactive lichenoid mixed population of lymphocytes with numerous intraepidermal Langerhans cells. This confirmed the diagnosis of the inflammatory stage of lichen sclerosus. The presence of prominent epithelioid Langerhans cells with activated small lymphocytes represents an immune response in LSA and could cause diagnostic confusion with neoplastic conditions. IHC staining can confirm cell type and rule out MF and extramammary Paget’s disease.

Exfoliative dermatitis

64-year-old man presented with a 3-week history of a diffuse, pruritic rash that had started on his trunk and then spread to his entire cutaneous surface, including the palms of his hands and soles of his feet. Physical examination revealed widespread fine scaling and diffuse erythema. Generalized lymphadenopathy was noted. No fever, hair loss, onycholysis, or nail shedding was detected. The patient had neither a personal history of skin disorders or, specifically, atopic eczema or psoriasis nor a family history of eczema or psoriasis. He also had no history of malignancy and was taking no medications. The patient's complete blood cell count with differential was unremarkable. He was treated with moisturizers, topical corticosteroids, and antihistamines and was advised to avoid possible irritants. One week later, the patient returned because of a worsening of his erythroderma. He also reported malaise and chills. Three 4-mm biopsy specimens were obtained from representative areas (ie, back, arm, and abdomen), and a 2-week course of oral corticosteroids was prescribed. The erythroderma greatly improved but worsened shortly after the steroid dose was tapered. The specimens showed psoriasiform hyperplasia with features suggestive of psoriasis vulgaris. The patient was treated with 25 mg of oral acitretin once a day. His erythroderma slowly resolved over 6 months, at which time the acitretin dose was tapered. The patient reported no recurrence of the erythroderma.

Interdigital psoriasis (psoriasis alba): Renewed attention for a neglected disorder

Interdigital psoriasis (psoriasis alba): Renewed attention for a neglected disorder

Psoriasin (S100A7) expression is altered during skin tumorigenesis.

BackgroundPsoriasin (S100A7) expression has previously been associated with psoriasiform hyperplasia as well as with tumor progression in breast cancer. Its expression profile for different stages of skin lesions is unknown. The aim of this study was to determine the relationship between psoriasin (S100A7) and tumor progression in skin.MethodsPsoriasin was assessed by immunohistochemistry and levels of expression determined by semi-quantitative scoring in skin biopsies from 50 patients. The cohort included normal skin, actinic keratosis, squamous carcinoma in-situ, invasive squamous cell carcinoma, and basal cell carcinoma.ResultsIn normal skin, psoriasin was rarely detected in epidermis but was expressed in underlying adnexae. In abnormal epidermis psoriasin was frequently expressed in abnormal keratinocytes in actinic keratosis, in-situ and invasive squamous cell carcinoma, but was rarely observed in the basal epidermal layer or in superficial or invasive basal cell carcinoma. The highest levels of expression were seen within squamous carcinoma in-situ. Significantly reduced levels of expression were observed in both unmatched (p = 0.0001) and matched (p < 0.004) invasive squamous cell carcinoma. Psoriasin expression within abnormal squamous lesions correlated with mitotic count (r = 0.54, p = 0.0036), however no significant relation was found with the intensity of dermal inflammatory cell infiltrates assessed within each pathology.ConclusionThese results suggest that altered psoriasin expression occurs in abnormal epidermis and that downregulation may be related to the onset of invasion in squamous cell carcinoma in skin.

Pityriasis lichenoides: A clonal T-cell lymphoproliferative disorder

Pityriasis lichenoides (PL) is a papulosquamous disorder often considered a form of reactive dermatosis and classified with small plaque parapsoriasis (digitate dermatosis). However, some patients with PL have developed large plaque parapsoriasis (LPP) and mycosis fungoides (MF), and lymphoid atypia and T-cell clonality have been reported in lesions of PL. We set out to explore the possibility that PL is a form of T-cell dyscrasia. Cases were selected by natural language search from an outpatient dermatopathology database; 35 cases were reviewed and clinicians and patients were contacted. Hematoxylin and eosin–stained sections were examined and immunophenotyping was carried out on paraffin-embedded, formalin-fixed tissue using antibodies to CD2, CD3, CD4, CD5, CD7, CD8, CD20, CD30, and CD56. In paraffin-embedded tissue, T-cell receptor (TCR)-γ chain rearrangement was sought through polymerase chain reaction single stranded conformational polymorphism analysis. There were 14 males and 21 females with a mean age of 40 years held clinically to have PL chronica (PLC) (28 cases) and/or PL et varioliformis acuta (PLEVA) (7 cases). Five patients developed large atrophic poikilodermatous and/or annular plaques compatible with MF and/or LPP in a background of typical PLC. All biopsies showed tropism of lymphocytes to an epidermis manifesting psoriasiform hyperplasia, dyskeratosis, parakeratosis, and intraepithelial collections of Langerhans' cells and lymphocytes mimicking Pautrier's microabascesses. Epidermal atrophy, dermal fibroplasia, poikilodermatous alterations, and a dominance of intraepidermal cerebriform cells were seen only in patients with chronic persistent disease (i.e., PLC) and in some cases corresponded with clinical progression to MF. All cases had a T cell–dominant infiltrate, with a CD7 deletion in 21 of 32 biopsies examined; the CD7-negative cells were typically the largest and most atypical forms, often in a cohesive array within the upper layers of the epidermis. In 17 biopsies in which a CD4 stain was satisfactory for evaluation, 50% or more of the intraepidermal population was CD4 positive in 8 biopsies, whereas in 11 biopsies 50% or more of the dermal infiltrate was CD4 positive. The CD4-positive cells frequently had a cerebriform nuclear morphology and were CD7 negative. Most cases had an admixture of CD8-positive lymphocytes in excess of 40% or more of the intraepidermal and/or dermal infiltrate; it was the dominant intraepidermal infiltrate in 10 cases. The CD8-positive cells, typically small, round, and CD7 positive, showed a directed pattern of migration into acrosyringia and suprapapillary plates, with satellitosis around CD4-positive/CD8-negative/CD7-negative atypical lymphocytes. CD56 positivity was seen among the intraepidermal lymphoid cells and roughly paralleled the CD8 profile. In general, CD8-positive lymphocytes dominated in cases of PLEVA, whereas CD4-positive lymphocytes were very conspicuous and composed the dominant intraepidermal populace only in those biopsies of progressive PL/PLC. Clonality was shown in 25 of 27 biopsies in which amplifiable DNA was obtained. Intraepithelial atypical lymphocytes, phenotypic abnormalities, and TCR-γ rearrangements suggest that PLC and PLEVA are a form of T-cell dyscrasia. Lesions may follow a recalcitrant course characteristic of MF and premycotic disorders such as LPP. The aberrant phenotype cell is similar to that defining MF: a CD4-positive T lymphocyte with a CD5 and CD7 deletion. Directed epidermal migration seen in biopsies procured from incipient lesions along with occasional temporal association to viral or drug exposure suggests that an abnormal immune response to an antigenic trigger may be the inciting event. HUM PATHOL 33:788-795. Copyright 2002, Elsevier Science (USA). All rights reserved.

Cutaneous manifestations of maternal engraftment in patients with severe combined immunodeficiency: a clinicopathologic study.

SCID is a heterogeneous group of disorders characterized by defective T cell and B cell function. Eczematous and morbilliform eruptions are common, and graft-versus-host disease (GVHD) due to maternal engraftment has been documented. We sought to better characterize SCID-related cutaneous disease observed prior to BMT and to compare the eruption to conventional GVHD. Medical records of 51 patients with SCID treated between 1982 and 1999 were reviewed. Ten of 51 (20%) had rash and evidence of maternal engraftment prior to BMT (study group). Eleven of 51 (22%) had no rash or evidence of engraftment pre-BMT but developed GVHD following transplant (control group). Skin biopsies were available for review for 8/10 of the study group and for 8/11 of the control group. Cutaneous findings consisted of a scaling, erythematous maculopapular eruption spread widely over the trunk and extremities, with near-erythroderma in some patients. Microscopically, biopsies from the study group differed significantly from controls. Key differences included parakeratosis (P < or = 0.01), psoriasiform hyperplasia (P < or = 0.04) and spongiosis (P < or = 0.04). The dermatopathologic findings of transplacental GVHD differ from the pattern of post-transplant GVHD. A 'psoriasiform-lichenoid-spongiotic' pattern with necrotic keratinocytes should trigger consideration of SCID and maternal engraftment in the dermatopathologic evaluation of eruptions of infancy.

A Clincopathologic Study

We report 9 patients with an unusual plasma cell proliferative disorder of the upper aerodigestive tract. Six patients were men and three, women. The age at presentation ranged from 40 to 67 years with a mean of 54 years. Symptoms at presentation included dysphonia, dysphagia, difficulty breathing, and oral pain. These plasma cell lesions typically produced a cobblestone or warty appearance of the upper aerodigestive tract mucosa including the larynx, pharynx, palate, lips, mouth, tongue, and trachea in varying combination of multiple sites in each patient. Histologically, all lesions were characterized by psoriasiform epithelial hyperplasia with dyskeratosis and dense subepithelial plasmacytosis. Plasma cells were mature but so expansive and diffuse in infiltration as to suggest extramedullary plasmacytoma. Immunohistochemistry for kappa and lambda light chain showed polyclonal immunoglobulin content in all cases examined. Microbial cultures and Warthin-Starry stains were negative for organisms. A variety of treatments including antibiotic therapy, corticosteroid administration, and surgical resection were unsuccessful. In two patients, the process required tracheostomy. This disorder has not been previously described with the exception of a single reported case, which is included in this series. The etiology, pathogenesis, and successful management of mucous membrane plasmacytosis remain unknown.

Detection of the Interferon-gamma-Induced Protein 10 in Psoriasiform Dermatitis of Acquired Immunodeficiency Syndrome

Interferon-gamma-induced protein 10 is a 10-kd protein produced by human keratinocytes following an exposure to interferon gamma. Keratinocytes within psoriatic plaques and within delayed-type hypersensitivity reactions have been shown to stain strongly with an affinity-purified rabbit antibody prepared against interferon-gamma-induced protein 10, suggesting a possible role for interferon gamma in the production of the lesions. A psoriasiform eruption has been seen in patients with acquired immunodeficiency syndrome (AIDS). Its severity appears to correlate with the degree of immunodeficiency in the early stages of AIDS. We stained 10 lesions of psoriasiform dermatitis of AIDS with the anti-interferon-gamma-induced protein 10 antibody using immunoperoxidase techniques. As controls, we studied 10 lesions of non-AIDS psoriasis, six lesions of seborrheic dermatitis with psoriasiform hyperplasia, one lesion of lichen simplex chronicus, and four biopsy specimens of normal skin from patients with AIDS. In addition, normal skin specimens taken from patients with AIDS and human immunodeficiency virus-negative patients at time of autopsy were examined. An identical, strong and diffuse staining pattern was seen in all cases of psoriasiform dermatitis of AIDS, non-AIDS psoriasis, seborrheic dermatitis, and lichen simplex chronicus. The specimens of normal skin showed only weak basal layer staining with anti-interferon-gamma-induced protein 10. Thus, the presence of interferon-gamma-induced protein 10 in keratinocytes was associated with psoriasiform hyperplasia and could be detected in both AIDS-associated and classic psoriasis.

Host-parasite relationships in hyperkeratotic (Norwegian) scabies: pathological and immunological findings

The dynamics of intraepidermal penetration of the scabies mite and the host's responses to the invaders have been studied in hyperkeratotic scabies. Contrary to the generally accepted view, the mites progressed not only through the stratum corneum but also into the underlying epidermis and even occasionally to the dermo-epidermal interface. Morphological evidence of reactive processes included parakeratosis surrounding the burrows, psoriasiform hyperplasia with increased basal cell labelling indices and exocytosis of mononuclear cells. 3H-Thymidine labelling indices of immunocompetent cells of the dermal infiltrate reached levels found in allergic patch test reactions and were in both cases higher than in non-immune-specific inflammatory processes. The labelling index of peripheral blood lymphocytes showed an increased ratio of B cells to T cells as compared to controls or patients with allergic contact dermatitis. Serum CIq fixation was higher than in untreated patients with common scabies. These results support our previous findings of immunological activation in host infested by the scabies mite.