Variety Of Inflammatory Dermatoses Research Articles

Inflammatory nail conditions. Part 1: nail changes in psoriasis.

Nail changes are visible in a variety of inflammatory dermatoses. The commonest dermatological condition with nail manifestations is chronic plaque psoriasis. This two-part article reviews the nail signs in psoriasis in Part 1, and the nail changes in cutaneous lichen planus and alopecia areata in Part 2. It provides a brief summary of the salient points in the clinical features, management and prognosis of these entities, with practical recommendations that may be beneficial to all dermatologists.

Clinicomorphological correlation of psoriasis and psoriasiform dermatitis

Introduction: Psoriasis is a chronic inflammatory skin disorder. Psoriasiform dermatitis on other hand is a frequently encountered terminology in a variety of inflammatory dermatoses. It often poses challenges to both dermatologists and pathologists alike. Clinical features when considered alone may not be reliable to differentiate psoriasis from psoriasiform dermatitis. Aims: (a)To correlate the clinicomorphological features of psoriasis and psoriasiform dermatitis. (b)To identify determinants that may contribute to the diagnosis of psoriasis and psoriasiform dermatitis. Methods: This is a prospective study of 40 cases. Cases clinically diagnosed as psoriasis and psoriasiform dermatitis were screened microscopically and as per morphological criterias 20 cases from each entity were selected and included in the study. Detailed histopathological analysis and correlation was done. Results: The clinical features of typical scales (p= 0.0012) and Auspitz's sign (p = 0.058) morphological evidence of regular acanthosis (p= 0.0005), absent granular layer (p = 0.0001) and presence of micromunros abscess (p=0.0001) were found to be statistically highly significant contributors to the diagnosis of psoriasis in comparison to psoriasiform hyperplasia. Other morphological features like suprapapillary thinning (p= 0.051) was also found to be morphologically significant. Vertical orientation of collagen bundles (p = 0.002) was found to be significantly associated with diagnosis of psoriasiform hyperplasia when compared to psoriasis. Conclusion: The present study reconfirms the diagnostic accuracy of scales, Auspitz’s sign as clinically reliable signs of psoriasis. However, in their absence, morphological presence of regular acanthosis, absent granular layer and Munro microabscess may contribute to the diagnosis of psoriasis. Similarly, vertical orientation of collagen bundles points toward a diagnosis of psoriasiform dermatitis. This may help clinicians not to miss the diagnosis of clinically insignificant psoriasis in order to start early treatment and prevent the poor prognosis in these patients.

P53 Is a Helpful Marker in Distinguishing Langerhans Cell Histiocytosis From Langerhans Cell Hyperplasia.

Langerhans cell histiocytosis (LCH) is a proliferative disorder of Langerhans cells that can be challenging to distinguish histologically from Langerhans cell (LC) hyperplasia, seen in a variety of inflammatory dermatoses. Lesional cells in both entities demonstrate positive staining for CD1a and S100. Previous studies have demonstrated positive staining of fascin, CD31, and p53 in cases of LCH, but currently, no studies have compared the staining profiles of these markers between LCH and LC hyperplasia. The authors compared immunohistochemical staining profiles of LCH (n = 15) and various inflammatory dermatoses with LC hyperplasia (n = 15) using fascin, CD31, and p53. Fascin, CD31, and p53 were graded as a percentage of CD1a staining cells in the epidermis and dermis of each specimen. Fascin showed no significant differences in staining between the 2 entities. CD31 was positive in the dermal infiltrate in 40% of cases of LCH and negative in all cases of LC hyperplasia. p53 was positive in the epidermal infiltrate in 50% of cases of LCH, and positive in the dermal infiltrate in 93% of cases of LCH, whereas negative in all cases of LC hyperplasia. Fascin was not a helpful marker in distinguishing LCH from LC hyperplasia. CD31, if positive in the dermal infiltrate, is suggestive of a diagnosis of LCH, but exhibits a relatively low sensitivity for this purpose. p53 proved to be a helpful and accurate diagnostic immunohistochemical stain when distinguishing between LCH and LC hyperplasia.

Histopathological spectrum of Psoriasiform dermatitis

Background: Psoriasiform dermatitis is a frequently encountered terminology in a wide variety of inflammatory dermatoses. It often poses challenges to both dermatologists and pathologists alike. Clinical features when considered alone may not be reliable, as they vary with both disease duration and treatment. On the contrary, histopathological material constitutes definite hard evidence, which can be preserved and will continue to be available for future review. The objective of the study is to study the histopathological findings in Psoriasiform dermatitis.Materials and Methods: This is a retrospective study in a tertiary care centre in Kerala, South India. All cases diagnosed as Psoriasis or mentioned as one of the differential diagnosis were included. The material included 66 skin biopsies. Patients with a previous diagnosis of the same were excluded from the study.Results: The lesions comprised 9% of the total number of skin biopsies. The age distribution pattern revealed that the highest percentage was in the 41-60 year age group (50%) with a male preponderance of 65%. Psoriasis was the most common lesion (60.60%) and Lichen simplex chronicus was the second most common lesion (10.60 %), encountered in the study.Conclusion: Some of the histopathological features are specific and characteristic for each entity like Psoriasis, Pityriasis rubra pilaris, Pityriasis rosea and Inflammatory linear verrucous epidermal nevus whereas some overlap in lesions like Prurigo nodularis, Lichen simplex chronicus and Allergic contact dermatitis. Hence, combination of proper clinical observation and histopathological study will give a conclusive diagnosis.

Clinical presentation and diagnostic delay in bullous pemphigoid: a prospective nationwide cohort

Prospective systematic analyses of the clinical presentation of bullous pemphigoid (BP) are lacking. Little is known about the time required for its diagnosis. Knowledge of the disease spectrum is important for diagnosis, management and inclusion of patients in therapeutic trials. The primary aims of the study were: (i) to characterize the clinical features of BP at time of diagnosis; and (ii) to assess the diagnostic delay in BP and its impact on prognosis All new cases of BP diagnosed in Switzerland between 1 January 2001 and 31 December 2002 were prospectively registered by means of a standardized data collection form. One hundred-seventeen patients with BP were included in the study. 97cases (82.9%) had typical features with vesicles, blisters and/or erosions at time of diagnosis, while in the remaining cases (17.1%) only excoriations, eczematous and/or urticarial infiltrated lesions were observed. Head/neck as well as palmo-plantar involvement were found in up to 20% of patients, while mucosal lesions were present in 14.5% of the cases. Diagnosis was made after a mean of 6.1 months after the first symptoms. In patients, in whom the diagnostic delay was 4 months or more (defined as late diagnosis group), lesions were more often limited to one body area. The type of lesions did not affect the diagnostic delay. Diagnosis was made more rapidly in patients with limb involvement compared to those without. The calculated mortality rate in the early and late diagnosis group was 18.9% and 17.9%, respectively, without significant difference. BP often presents with bullous lesions at time of diagnosis after a mean diagnostic delay of 6 months. Nevertheless, up to 20% of patients lack obvious blistering and postbullous erosions, mimicking thus a variety of inflammatory dermatoses. Localized disease is associated with an increased diagnostic delay, which has however no impact on prognosis.

The use of infliximab in dermatology

Autoimmune diseases like Crohn's disease, rheumatoid arthritis (RA) and psoriasis are often difficult to treat due to complex underlying immunologic pathways. Tumor necrosis factor (TNFalpha) is an important proinflammatory cytokine that seems to play an important role in the pathogenesis of these diseases. After the approval of a variety of drugs which block the biological activity of TNFalpha, new therapeutic options were available and especially infliximab became widely used. TNFalpha, as a member of the proinflammatory cytokine family, is a major cytokine in different inflammatory dermatological diseases such as cutaneous vasculitis, lupus erythematosus, eczema or psoriasis. Therefore infliximab has been used in a variety of inflammatory dermatoses lately, sometimes with great success. Several case reports showing new indications for a successful use of TNFalpha-inhibitors in dermatology have been published and will be reviewed in the following article. Nevertheless, infliximab is not approved for these indications at the moment and has to be considered as off-label use.

Use of in situ detection of histone mRNA in the assessment of epidermal proliferation: comparison with the Ki67 antigen and BrdU incorporation

The labelling index is commonly used as a measure of proliferation. However, the use of tritiated thymidine or BrdU labelling of S-phase cells is limited to prospective samples. We have employed an oligonucleotide cocktail complementary to the mRNA species encoding the replication-dependent histones H2B, H3 and H4 for non-isotopic in situ hybridization (NISH), and have compared the resultant proliferation indices in normal skin with those obtained by bromodeoxyuridine (BrdU) incorporation and by Ki67 immunohistochemistry (IHC) using the monoclonal antibody MIB1. In addition, we compared the staining characteristics of histone NISH and Ki67 IHC in a further 25 samples from a variety of inflammatory dermatoses and neoplastic conditions, as well as from normal skin. In normal skin, S-phase (histone NISH and BrdU) and cycling (Ki67) cells were confined to the basal and low suprabasal layers. The labelling indices determined by histone NISH and BrdU incorporation were similar, whereas that of Ki67 IHC was four times greater. In biopsies from hyperproliferative dermatoses and dysplastic or malignant lesions, the number of histone NISH- and Ki67 IHC-positive cells was generally elevated; in accordance with the differential expression of these two markers during the cell cycle, MIB1 consistently gave higher results. The advantage of histone NISH over Ki67 IHC is that it is a marker of the same part of the cell cycle as BrdU incorporation. However, the combined use of both histone NISH and Ki67 IHC to measure two cell cycle parameters, namely S-phase and the number of cycling cells, allows more detailed retrospective study of epidermal proliferation than has been possible previously.

Lnterleukin-8 Production from Cultured Human Dermal Fibroblasts by Stimulation with Supernatant of Cultured Human Epidermal Cells

There is much evidence to support the theory that keratinocytes and dermal fibroblasts actively participate in inflammatory reactions by the production of proinflammatory mediators or cytokines. We investigated the neutrophil chemotactic activity in conditioned media of cultured epidermal cells and dermal fibroblasts, and found that an epidermal cell-derived factor induced fibroblasts to produce a neutrophil chemotactic factor. This neutrophil chemotactic factor was identified as interleukin-8 (IL-8) by the elution position on HPLC and by a neutralization test that uses monoclonal anti-IL-8 antibody (14E4). The epidermal cell-derived factor was fractionated together with thymocyte-proliferating activity on Sephadex G-75 gel chromatography followed by HPLC. It was blocked specifically by anti-interleukin-1 (IL-1) alpha antibody, which indicates that this factor was IL-1 alpha. Since a variety of inflammatory dermatoses is characterized by the infiltration of neutrophils into the skin, induction of IL-8 production in fibroblasts by epidermal cells may play an important role in inflammatory skin diseases.

Enhanced antibody titers to an oxidized DNA base in inflammatory and neoplastic diseases.

Reactive oxygen species (ROS) produced by phagocytic cells induce oxidative stress during chronic inflammation. ROS play a role in the pathogenesis of a broad range of diseases including autoimmune, cardiac and neoplastic abnormalities. We found that sera of patients with a variety of inflammatory dermatoses contain elevated levels of antibodies (Ab) binding to an oxidized DNA base derivative, 5-hydroxymethyl-2'deoxyuridine (HMdU) coupled to bovine serum albumin, as determined by the enzyme-linked immunosorbent assay. Patients with immune complex diseases and a history of neoplasm elaborated the highest titers of anti-HMdU Ab. Titers from sera of psoriatic subjects were lower than from the aforementioned groups but were still significantly elevated (p < 0.001) above those of healthy controls. Treatment of inflammatory dermatoses with systemic antiinflammatory and cytotoxic drugs significantly lowered the titers [p < 0.005 (immune complex) or p < 0.001 (psoriasis and neoplastic) diseases], suggesting that this assay may be of value in monitoring the response to therapy in these diseases.

T-cell inducer populations in cutaneous inflammation: a predominance of T helper-inducer lymphocytes (THi) in the infiltrate of inflammatory dermatoses

The mononuclear infiltrate found in a variety of inflammatory dermatoses was characterized by a predominance of T helper-inducer lymphocytes (THi), CD4+/CD45RA-/CD45RO+, a population of cells responsible for maintaining and promoting immune reactions. Only small numbers of T-suppressor-inducer lymphocytes (TSi), CD4+/CD45RA+/CD45RO-, cells responsible for inducing CD8 suppressor-effector cells to 'down regulate' immune reactions, were seen. The predominance of CD4+ THi lymphocytes was common to all dermatoses studied and suggests a common final pathway in chronic cutaneous inflammation, irrespective of initial causative factors.

Cyclosporin A in the Treatment of Lichen Planus

To the Editor.— Cyclosporin A has now been successfully used in a variety of inflammatory dermatoses, 1-3 although the mechanism of action remains obscure and may not be related to the drug's potent immunosuppressive properties. Lichen planus (LP) is a disease that is characterized by a predominantly T-cell inflammatory infiltrate,4 and, whether cyclosporin A acts via its selective inhibition of T-lymphocyte proliferation 5 or by some other as yet unknown mechanism, it seemed appropriate to assess the response of patients with LP to cyclosporin A. Eight patients (six men, two women; age range, 35 to 63 years) with widespread histologically proven LP (mean duration, 4.47 years [SEM ± 2.2]) were treated with oral cyclosporin A, 5 mg/kg per day. All patients were normotensive with normal serum creatinine levels prior to treatment. No concurrent topical therapy was used. Patients were seen at 2-week intervals for full clinical assessment, whole-blood cyclosporin level (12