Defining cancer risk in dermatomyositis. Part I

The idiopathic inflammatory myopathies (IIMs) comprise polymyositis, myositis overlapping with another connective tissue disease, dermatomyositis (DM) and inclusion-body myositis (IBM). IIMs are characterized by the presence of proximal muscle weakness, increased levels of muscle-specific enzymes, specific electromyographic abnormalities, and the presence of inflammatory cell infiltrates in skeletal muscle. Clinical, serological and histological criteria can be used to define individual IIM subtypes. In the first of this two-part review series, we examine the evidence for the existence of cancer-associated myositis (CAM), and in part 2, we discuss recent discoveries that provide insight into identification of patients with DM, who may be most at risk of developing CAM.     

Evaluation and Management of Polymyositis

Polymyositis (PM) is one of the inflammatory myopathies, disorders characterized pathologically by the presence of inflammatory infiltrates in striated muscle. The principal clinical manifestation of PM is proximal muscle weakness. The cause of PM is unknown, but current evidence suggests that it is an autoimmune disorder. PM can affect people of any age, but most commonly presents between the ages of 50 to 70. PM is rarely seen in people younger than 18 years of age, and is twice as common among females than males. PM is more common in blacks than in whites. The overall prevalence of PM is 1 per 100,000. Muscle weakness may develop suddenly or more insidiously over a period of weeks to months. The classic symptom of PM is proximal weakness, which may manifest as difficulty holding the arms over the head, climbing stairs, or rising from a chair. Weakness of the striated muscle of the upper esophagus may result in dysphagia, dysphonia, and aspiration. The chest wall muscles may be affected, leading to ventilatory compromises. Involvement of cardiac muscle may lead to arrhythmias and congestive heart failure. Dermatomyositis (DM) is closely related to PM, and both are distinguished primarily by the occurrence of characteristic skin abnormalities in the former. PM and DM may be associated with a variety of malignancies. PM may also occur as part of the spectrum of other rheumatic diseases like systemic lupus erythematosus and mixed connective tissue disease. Moreover, inflammatory myopathy may be caused by some drugs (procainamide, D-penicillamine), and viruses, most notably the retroviruses. Corticosteroids and immunosuppressive agents are the mainstays of therapy for PM. The principal goals of therapy are to improve strength and improve physical functioning. Many patients require treatment for several years. The 5-year survival rate for treated patients is in the order of 95%. Up to one-third of PM patients may be left with some degree of residual muscle weakness.     

免疫因素在特发性炎症性肌病中的作用机制

特发性炎症性肌炎包括多发性肌炎,皮肌炎及包涵体肌炎,是一组以肌肉组织的炎细胞浸润,肌无力为主要特点,浸润的炎细胞是以T淋巴细胞和巨噬细胞为主,个别也有B淋巴细胞。本文主要综述了T、B淋巴细胞、DC及其它APCs在IIMs中的病理生理作用。     

Clinical Presentation and Evaluation of Dermatomyositis

Dermatomyositis (DM) is a chronic inflammatory disorder of the skin and muscles. Evidence supports that DM is an immune-mediated disease and 50–70% of patients have circulating myositis-specific auto-antibodies. Gene expression microarrays have demonstrated upregulation of interferon signaling in the muscle, blood, and skin of DM patients. Patients with classic DM typically present with symmetric, proximal muscle weakness, and skin lesions that demonstrate interface dermatitis on histopathology. Evaluation for muscle inflammation can include muscle enzymes, electromyogram, magnetic resonance imaging, and/or muscle biopsy. Classic skin manifestations of DM include the heliotrope rash, Gottron''s papules, Gottron''s sign, the V-sign, and shawl sign. Additional cutaneous lesions frequently observed in DM patients include periungual telangiectasias, cuticular overgrowth, “mechanic''s hands”, palmar papules overlying joint creases, poikiloderma, and calcinosis. Clinically amyopathic DM is a term used to describe patients who have classic cutaneous manifestations for more than 6 months, but no muscle weakness or elevation in muscle enzymes. Interstitial lung disease can affect 35–40% of patients with inflammatory myopathies and is often associated with the presence of an antisynthetase antibody. Other clinical manifestations that can occur in patients with DM include dysphagia, dysphonia, myalgias, Raynaud phenomenon, fevers, weight loss, fatigue, and a nonerosive inflammatory polyarthritis. Patients with DM have a three to eight times increased risk for developing an associated malignancy compared with the general population, and therefore all patients with DM should be evaluated at the time of diagnosis for the presence of an associated malignancy. This review summarizes the immunopathogenesis, clinical manifestations, and evaluation of patients with DM.     

Folliculitis et perifolliculitis capitis abscedens et suffodiens controlled with a combination therapy: systemic antibiosis (metronidazole plus clindamycin), dermatosurgical approach, and high-dose isotretinoin

Folliculitis et perifolliculitis capitis abscedens et suffodiens is a rare disease of unknown etiology. It is a suppurative process that involves the scalp, eventually resulting in extensive scarring and irreversible alopecia. The condition is also known as 'acne necrotica miliaris' or 'Proprionibacterium' folliculitis. Most often the disease affects men of African-American or African-Caribbean descent between 20 and 40 years of age. The clinical picture is determined by fluctuating painful fistule-forming conglomerates of abscesses in the region of the occipital scalp. The cause of scalp folliculitis is not well understood. It is generally considered to be an inflammatory reaction to components of the hair follicle, particularly the micro-organisms. These include: bacteria (especially Propionibacterium acnes, but in severe cases, also Staphylococcus aureus), Yeasts (Malassezia species) and mites (Demodex folliculorum). The initial histopathologic finding is an exclusively neutrophilic infiltration followed by a granulomatous infiltrate. The treatment of the disease is usually difficult and often disappointing. Successful treatment with isotretinoin 1 mg/kg body mass could be achieved only after regular systematic administration in the course of 3-4 months. Here we describe a patient with eruptive purulent form of the disease, which has been controlled with combination therapy: systemic antibiosis with metronidazole and clindamycin, dermatosurgical removal of single nodular formations, and isotretinoin 1 mg/kg body mass for 3-5 months.     

Nuevos autoanticuerpos en la dermatomiositis

Dermatomyositis is an idiopathic inflammatory myopathy that affects skeletal muscle and the skin. Idiopathic inflammatory myopathies are characterized by the production of autoantibodies directed against different cell structures. Some of these autoantibodies are specific to idiopathic inflammatory myopathies (myositis-specific antibodies) whereas others are found in a range of overlap syndromes (myositis-associated antibodies). Although they are all associated with certain clinical and physiopathological characteristics of myositis, myositis-specific antibodies are essentially the most useful markers for clinical diagnosis, classification, and prognosis in idiopathic inflammatory myopathies. In recent years, two new myositis-specific antibodies—in clinically amyopathic dermatomyositis (CADM), CADM-140 and, in cancer-associated dermatomyositis, anti-p155/p140— have been identified. This is of great importance as no myositis-specific antibodies had previously been detected in these clinical subgroups. The identification of target antigens that are recognized by these antibodies is essential for a better understanding of the pathogenesis of these diseases.     

A Study of Correlation Between Clinical and Histopathological Findings of Erythroderma in North Bengal Population

Background:

Erythroderma is a reaction pattern characterized by erythema and desquamation of 90% or more body surface area along with some metabolic alterations.

Materials and Methods:

Here we studied 32 patients of erythroderma at of North Bengal Medical College for a period of 1 year to find the etiology, clinical features and histological changes. Detailed history was taken from all the patients followed by relevant biochemical investigations and histological examination. To correlate the clinical and histopathological findings chi square test was used.

Results:

Male preponderance was present and most of them were in the 4^th or 5^th decade. Etiologically the patients were divided into secondary erythroderma developing over pre-existing dermatoses, and idiopathic erythroderma. Secondary erythroderma (n = 24) cases outnumbered the idiopathic cases (n = 8). Among the pre-existing dermatoses, psoriasis was found to be the most common etiologic agent. Apart from erythema the other common presenting features were scaling and itching. Histopathological categorization was possible in 59.3% cases, rest of the cases showed non-specific dermatitis. The most common histopathologic diagnosis was psoriasis (21.8% of cases).

Conclusions:

Our study of clinicopathological correlation of erythroderma patients among north bengal population corroborates with most of the previous studies done in other areas. As ours is a cross-sectional study in a undefined population so we could not determine the true incidence of erythroderma in north bengal population. We might have missed lymphoma as a cause of erythroderma in idiopathic cases due to lack of long follow-up, so we understand that further studies over a defined population with long follow-up is needed to determine the true incidence and causes of idiopathic erythroderma.     

Role of In Vivo Reflectance Confocal Microscopy in Determining Stability in Vitiligo: A Preliminary Study

Background:

Vitiligo is an acquired pigmentary disorder. In vivo reflectance confocal microscopy (RCM) reproducible imaging technique has already been reported to be useful in the diagnosis of other skin diseases.

Objective:

To define RCM features of vitiligo on different clinical stages.

Materials and Methods:

A total of 125 patients with a clinical diagnosis of vitiligo were included in this study. After informed consent, lesional skins of those vitiligo patients were characterized by using RCM. Five patients with inflammatory cell infiltration observed at the edge of skin lesions and another 5 patients without inflammatory cell infiltration were selected. Biopsies were performed at same sites of the RCM examination areas for histological and immune-histological analysis.

Results:

In the active stage of vitiligo, the RCM examination revealed that the bright dermal papillary rings presented at the dermoepidermal junction level in normal skin lost their integrity or totally disappeared, border between vitiligo lesion and normal skin became unclear, and highly refractile cells that referred to infiltrated inflammatory cells could be seen within the papillary dermis at the edge of the lesions. In the stable stage of vitiligo, the RCM showed a complete loss of melanin in lesional skin and a clear border between lesional and normal skin.

Conclusion:

A simple clinical examination with RCM may reliably and efficiently allow evaluation of the stability status of vitiligo lesions.     

Epidemiology and clinical features of atopic dermatitis in India

Literature on atopic dermatitis (AD) has experienced a spurt in the recent years with interest on genetics, immunology, pathogenesis, psychological impact, development of newer more effective and safer treatment agents. Indian literature on AD is limited, probably due to lower prevalence, and milder disease. In this review, we have discussed the Indian literature on epidemiology and clinical features of AD.     

mTOR Signaling Cascade in Psoriatic Disease: Double Kinase mTOR Inhibitor a Novel Therapeutic Target

In this short communication we are providing insight about the regulatory role of the phosphatidylinositol 3-kinase (PI3K)-AKT-mammalian target of rapamycin (mTOR) kinase system in psoriatic disease. This is an upcoming active research field in respect to elucidating the inflammatory and proliferative cascades of psoriatic disease. To provide a new dimension to the understandings of the molecular principles of the pathogenesis of autoimmune diseases, we hypothesized that (i) dysregulation of cytokines and growth factors in autoimmune diseases activate the mTOR signaling system and (ii) the activated mTOR kinase system is a key regulator of the inflammatory/proliferative cascades of the disease process. In support of this hypothesis we have earlier reported that growth factors (nerve growth factor (NGF) and platelet-derived growth factor (PDGF)) and relevant cytokines (interleukin (IL)-17, IL-22) known to be critical for psoriasis, psoriatic arthritis, and rheumatoid arthritis activate the mTOR signaling system. Here, we are providing our latest observations that the mTOR signaling proteins are upregulated in psoriatic skin and further we observed that proliferation of keratinocytes (KC) and synovial cells (synovial fibroblasts (FLS)) of psoriatic arthritis are dependent on the PI3K-AKT-mTOR kinase system. To our knowledge, we are the first to explore whether a double kinase inhibitor of mTOR signal proteins has a therapeutic potential for psoriatic disease. Here we will be sharing our views, our research work in this field and as well we will provide evidences how a double kinase inhibitor of mTOR signal proteins can be an effective therapeutic agent for psoriatic disease.     

UNDIAGNOSED DIABETES MELLITUS IN PATIENTS WITH HERPES ZOSTER

Background:

Herpes Zoster (HZ) is reactivation of latent varicella-zoster virus that involves dermatomes. Aging and immunosupressed states are among the main risk factors. Some investigations showed that HZ is more common in diabetic patients than in normal population.

Aim:

To determine whether undiagnosed DM is more common in patients with HZ than in those without it.

Materials and Methods:

In this study 103 patients with HZ (cases) and 142 as control participated. They had no history of DM. Both groups were matched according to age, gender and family history of DM. Fasting plasma glucose was checked for all participants. DM was defined when the fasting plasma glucose was equal or more 126 mg/dl.

Results:

35.9% of patients with HZ and 19.7% of the control group had DM. There was significant association between HZ and undiagnosed DM (OR = 2.28, 95% CI: 1.28–4.06).

Conclusion:

Our findings indicate that the prevalence of undiagnosed DM is more common in HZ patients and supports the policy to investigate patients with HZ for the presence of undiagnosed DM.     

Oral Lichen Planus: An Update on Etiology,Pathogenesis, Clinical Presentation,Diagnosis and Management

The mouth is a mirror of health or disease, a sentinel or early warning system. The oral cavity might well be thought as a window to the body because oral manifestations accompany many systemic diseases. In many instances, oral involvement precedes the appearance of other symptoms or lesions at other locations. Oral lichen planus (OLP) is a chronic mucocutaneous disorder of stratified squamous epithelium of uncertain etiology that affects oral and genital mucous membranes, skin, nails, and scalp. LP is estimated to affect 0.5% to 2.0% of the general population. This disease has most often been reported in middle-aged patients with 30-60 years of age and is more common in females than in males. The disease seems to be mediated by an antigen-specific mechanism, activating cytotoxic T cells, and non-specific mechanisms like mast cell degranulation and matrix metalloproteinase activation. A proper understanding of the pathogenesis, clinical presentation, diagnosis of the disease becomes important for providing the right treatment. This article discusses the prevalence, etiology, clinical features, oral manifestations, diagnosis, complications and treatment of oral LP.     

A clinical evaluation of skin tags in relation to obesity, type 2 diabetis mellitus, age, and sex

Background:

Skin tags (STs) have been investigated as a marker of type 2 diabetes mellitus (DM), yet the relation of STs to obesity is still a matter of controversy.

Aim:

The aim of the study is to explore the relation of number, size and color of STs to obesity, diabetes, sex and age in one study.

Methods:

The study included 245 nondiabetic (123 males and 122 females) and 276 diabetic (122 males and 154 females) subjects. We recorded age, sex, body mass index (BMI), relevant habits, STs color, size, and number in different anatomical sites.

Results:

The presence and the mean number of STs was more in obese than nonobese participants (P = 0.006 and P < 0.001, respectively) and was not affected by sex. However, the number increased significantly with age. The presence of mixed-color STs was related to obese (P < 0.001) participants. Multivariate logistic regression revealed that only BMI was significantly associated with the mixed-color STs (OR = 3.5, P < 0.001). The association of DM (OR = 1.7) with mixed-color STs was nonsignificant (P = 0.073). Neither age nor sex had any association with mixed-color STs. Within cases that developed mixed-color STs, the multivariate analysis showed that only BMI had a significant correlation to the number of STs (beta = 0.256, P = 0.034).

Conclusion:

The study showed that not only the number but also the presence of mixed-color ST was related to obesity, but not to diabetes. The presence of mixed-color STs in nondiabetic subjects needs close inspection of BMI.     

Pemphigus Foliaceus Masquerading as IgA Pemphigus and Responding to Dapsone

A 14-year-old male presented with seven years history of recurrent episodes of fluid filled, itchy and eroded lesions over the body not responding to oral corticosteroids and azathioprine. Dermatological examination revealed crusted plaques and erosions in a seborrheic distribution. Histopathology of skin lesions and direct immunofluorescence were characteristic of pemphigus foliaceus. He was treated with dexamethasone pulse therapy with inadequate response. However, relapsing skin lesions revealed a circinate arrangement with a predilection to trunk and flexures. In view of clinical features suggestive of IgA pemphigus, he was started on dapsone, to which he responded dramatically in four weeks. However, repeat biopsy continued to reveal features of pemphigus foliaceus and ELISA for anti-desmoglein 1 antibodies was positive.     

Evaluation of Clinical Significance of Dermoscopy in Alopecia Areata

Background:Alopecia areata (AA) is a common, chronic inflammatory disease characterized by nonscarring hair loss on the scalp or any hair-bearing area of the body. Recently, dermoscopy, a noninvasive diagnostic procedure, has been employed for the diagnosis of AA.Aim:To evaluate various dermoscopic patterns in AA and correlate these patterns with the disease activity and severity.Results:A total of fifty patients of AA were recruited in the study. Female outnumbered males with the ratio being 1.173:1. Mean age of the patients was 25.06 years. Mean duration of disease was 14 months. The most common site involved was scalp (80%) and type noted was patchy (84%). Various dermoscopic patterns noted were yellow dots (YD) (88%), short vellus hair (66%), black dots (BD) (58%), broken hairs (BHs) (56%), tapering hair (TH) (26%), Coudability hairs (14%), pigtail hair (14%), and Pohl-Pinkus constrictions (2%). Statistically significant correlation was observed between BD, BHs, THs, and disease activity. No significant correlation was found between severity and any of the dermoscopic features.Conclusion:The most common dermoscopic pattern in our study was YD. Presence of BDs, BHs, and THs indicate active disease. Dermoscopic patterns were not affected by severity of the disease.     

Understanding and Evaluating Systematic Reviews and Meta-analyses

A systematic review is a summary of existing evidence that answers a specific clinical question, contains a thorough, unbiased search of the relevant literature, explicit criteria for assessing studies and structured presentation of the results. A systematic review that incorporates quantitative pooling of similar studies to produce an overall summary of treatment effects is a meta-analysis. A systematic review should have clear, focused clinical objectives containing four elements expressed through the acronym PICO (Patient, group of patients, or problem, an Intervention, a Comparison intervention and specific Outcomes). Explicit and thorough search of the literature is a pre-requisite of any good systematic review. Reviews should have pre-defined explicit criteria for what studies would be included and the analysis should include only those studies that fit the inclusion criteria. The quality (risk of bias) of the primary studies should be critically appraised. Particularly the role of publication and language bias should be acknowledged and addressed by the review, whenever possible. Structured reporting of the results with quantitative pooling of the data must be attempted, whenever appropriate. The review should include interpretation of the data, including implications for clinical practice and further research. Overall, the current quality of reporting of systematic reviews remains highly variable.     

Follicular Porokeratosis at alae Nasi; A Case Report and Short Review of Literature

Porokeratosis are disorders of keratinization, characterized histologically by a parakeratotic column, the cornoid lamellae, and clinically by a distinct peripheral ridge. Porokeratosis usually occurs on the trunk or extremities, and facial lesions are rare. Follicular involvement, identified by follicular localization of cornoid lamellae, is uncommon and described only in association with disseminated superficial actinic porokeratosis (DSAP) and porokeratosis Mibelli (PM). A 34-Year- old woman is presented with asymptomatic 1 cm plaque lesion with hyperkeratotic ridge and depressed center on her nose since three years. Histopathological examination of a biopsy revealed cornoid lamellae confined exclusively to the follicle.