Oral Lichenoid Lesions - A Review and Update

Background:

Oral lichenoid lesions or reactions (OLLs/OLRs) are clinical and histological contemporaries of the classical oral lichen planus (OLP) that have generated a lot of debate in literature. In contrast to the idiopathic nature of OLP, OLLs are often associated with a known identifiable inciting factor. A superficial examination of these lesions clinically and histologically often reveals many similarities with OLP, but recent data indicate that distinguishable features do exist and form the basis of most classifications.

Aims and Objectives:

This paper attempts to collate available data in English literature on OLLs, highlight distinguishing features clinically and histologically and reflect on the malignant transformation potential and treatment modalities of the condition.

Materials and Methods:

A comprehensive search of medical and dental databases including PubMed, Ovid, Cochrane, Pubget, Researchgate, and non-medical search engines were utilized for the review. The search words included “oral lichen planus”, “oral lichenoid lesions”, “oral drug reactions”, “lichenoid dysplasia”, and “adverse effects of dental materials”.

Review Results:

OLLs seem to grossly underrated and most cases were clubbed as OLP. Definite clinical and histological features were uncovered to establish the identity of this lesion. Associations with dental restorative materials, drugs, and medications have been conclusively proven in the etiology of this condition. Specific markers are being utilized to diagnose the condition and monitor its progress.

Conclusion:

Substantial differentiating features were uncovered to delineate OLLs as a separate entity with definite etiology, pathogenesis, and a high malignant transformation rate compared with OLP.     

Target-like Pigmentation After Minipunch Grafting in Stable Vitiligo

Surgical treatment for vitiligo has been ever evolving. Each surgical modality has its own benefits and limitations. Miniature punch grafting is the most extensively performed surgery, which gives good results in stable vitiligo. Herein we report an unusual type of repigmentation observed after minipunch grafting in a patient of stable vitiligo, which resembled target-like lesions with a “perigraft halo” surrounding individual grafts. Such pigment spread occurred despite the use of 0.5 mm larger graft from the donor site.     

Atypical Cutaneous Sporotrichosis in an Immunocompetent Adult: Response to Potassium Iodide

Cutaneous sporotrichosis, also known as “Rose Gardener''s disease,” caused by dimorphic fungus Sporothrix schenkii, is usually characterized by indolent nodular or nodulo-ulcerative lesions arranged in a linear pattern. We report bizarre nonlinear presentation of Sporotrichosis, in an immunocompetent adult occurring after a visit to Amazon rain forest, speculating infection with more virulent species of Sporothrix. The diagnosis was reached with the help of periodic acid-Schiff positive yeast cells and cigar shaped bodies seen in skin biopsy along with the therapeutic response to potassium iodide.     

Allergic Contact Dermatitis (Type IV Hypersensitivity) and Type I Hypersensitivity Following Aromatherapy with Ayurvedic Oils (Dhanwantharam Thailam,Eladi Coconut Oil) Presenting as Generalized Erythema and Pruritus with Flexural Eczema

Herbal and Ayurvedic medications, believed to be “mild” and “natural” are usually sought as the first line of treatment before resorting to “stronger” allopathic medication. There are very few reports of adverse reactions to either topical and/or systemic Ayurvedic medications. Massage aromatherapy with ayurvedic oils plays an important role in alleviation of pain, but may cause allergic contact dermatitis. This is the second case report of allergic contact dermatitis to ayurvedic oil.     

Secondary Syphilid Developing Over Healed Lesions of Varicella: Wolf's Isotopic Response?

Isotopic response is a distinctive phenomenon in which a new skin disorder occurs at the site of another, unrelated, and already healed skin disease. Most of the cases documented in the literature were associated with herpes zoster as primary disease while the list of “second” diseases is quite long. We report here a hitherto unreported occurrence of isotopic response in which secondary syphilis occurred on the healed lesions of varicella.     

Comparison of Bacillary Index on Slit Skin Smear with Bacillary Index of Granuloma in Leprosy and its Relevance to Present Therapeutic Regimens

Background:

As the world moves toward elimination of leprosy, persistence of infective cases in endemic pockets remains a significant problem. The use of clinical criteria to decide the paucibacillary (PB) versus multibacillary (MB) regimens has greatly simplified therapy at the field setting. However, a small but significant risk of under-treatment of so-called “PB” cases which actually have significant bacillary load exists. This study was undertaken to assess this risk and compare two methods of assessment of bacillary load, namely bacillary index on slit skin smear (BIS) versus bacillary index of granuloma (BIG).

Aims:

To compare BIS with BIG on skin biopsy in consecutive untreated cases of leprosy.

Materials and Methods:

This prospective study was conducted over a period of 12 months, wherein new untreated patients with leprosy were consecutively recruited. After a thorough clinical examination, each patient underwent slit skin smear (SSS) where the BIS was calculated. The same patient also underwent a skin biopsy from a clinical lesion where, the BIG was calculated. SSS and skin biopsy for BIS and BIG respectively were repeated for all patients at the end of therapy for comparison. All patients received therapy according to World Health Organization-Multidrug Therapy Guidelines.

Results:

The BIG was positive in all cases where the BIS was positive. Significantly, BIG was positive in three cases of borderline tuberculoid leprosy with <5 lesions who received PB regimen, whereas the BIS was negative in all three cases.

Conclusion:

This study suggests that BIG may be a better indicator of the true bacillary load in leprosy as compared to BIS. Its role in management is significant, at least in tertiary care centers to prevent “under-treatment” of so called PB cases, which may actually warrant MB regimens.     

Unmasking Diogenes Syndrome

Diogenes syndrome is characterized by extreme self-neglect, social withdrawal, and poor personal and domestic hygiene. We report a case of Diogenes syndrome presenting with dermatitis passivata. An unusual “mask” of dirt resembling a carapace, onset of neglect after awareness of a breast lump and resumption of personal grooming and social activities after removal of the lump and counseling were seen.     

Malassezia—Can it be Ignored?

Genus Malassezia comprises of 14 species of “yeast like fungi,” 13 of which are lipophilic and 1 is nonlipophilic. They are known commensals and in predisposed individuals they commonly cause a spectrum of chronic recurrent infections. They rarely also cause serious illnesses like catheter-related blood stream infections, CAPD associated peritonitis etc., Though these fungi have been known to man for over 150 years, their fastidious nature and cumbersome culture and speciation techniques have restricted research. Since the last taxonomic revision, seven new species have been added to this genus. Their ability to evade the host immune system and virulence has increased the spectrum of the diseases caused by them. These agents have been implicated as causal agents in common diseases like atopic dermatitis recently. Though culture-based research is difficult, the new molecular analysis techniques and facilities have increased research in this field such that we can devote more attention to this genus to study in detail, their characteristics and their growing implications implications in the clinical scenario.     

Wolf's Isotopic Response: Report of a Case and Review of Literature

“Wolf''s isotopic response” refers to the occurrence of a new dermatosis at the site of previously healed dermatosis. A number of factors including viral, neural, vascular, and immunologic factors have been implicated in the causation of this peculiar response but none has been proven conclusively. Here, we report a case where lichen planus developed at the site of dermatofibrosarcoma protruberans that had been previously treated with surgery and radiotherapy. We also put forth a hypothesis on the genesis of isotopic response considering the above mentioned factors.     

Biostatistics Series Module 2: Overview of Hypothesis Testing

Hypothesis testing (or statistical inference) is one of the major applications of biostatistics. Much of medical research begins with a research question that can be framed as a hypothesis. Inferential statistics begins with a null hypothesis that reflects the conservative position of no change or no difference in comparison to baseline or between groups. Usually, the researcher has reason to believe that there is some effect or some difference which is the alternative hypothesis. The researcher therefore proceeds to study samples and measure outcomes in the hope of generating evidence strong enough for the statistician to be able to reject the null hypothesis. The concept of the P value is almost universally used in hypothesis testing. It denotes the probability of obtaining by chance a result at least as extreme as that observed, even when the null hypothesis is true and no real difference exists. Usually, if P is < 0.05 the null hypothesis is rejected and sample results are deemed statistically significant. With the increasing availability of computers and access to specialized statistical software, the drudgery involved in statistical calculations is now a thing of the past, once the learning curve of the software has been traversed. The life sciences researcher is therefore free to devote oneself to optimally designing the study, carefully selecting the hypothesis tests to be applied, and taking care in conducting the study well. Unfortunately, selecting the right test seems difficult initially. Thinking of the research hypothesis as addressing one of five generic research questions helps in selection of the right hypothesis test. In addition, it is important to be clear about the nature of the variables (e.g., numerical vs. categorical; parametric vs. nonparametric) and the number of groups or data sets being compared (e.g., two or more than two) at a time. The same research question may be explored by more than one type of hypothesis test. While this may be of utility in highlighting different aspects of the problem, merely reapplying different tests to the same issue in the hope of finding a P < 0.05 is a wrong use of statistics. Finally, it is becoming the norm that an estimate of the size of any effect, expressed with its 95% confidence interval, is required for meaningful interpretation of results. A large study is likely to have a small (and therefore “statistically significant”) P value, but a “real” estimate of the effect would be provided by the 95% confidence interval. If the intervals overlap between two interventions, then the difference between them is not so clear-cut even if P < 0.05. The two approaches are now considered complementary to one another.     

Margins in Skin Excision Biopsies: Principles and Guidelines

Skin biopsies are usually undertaken to confirm a clinical diagnosis, to remove a lesion, and to determine the adequacy of excised tissue margin. A surgical margin is technically defined as the “edge” of the tissue removed. The term is especially pertinent when the tissue excised is suspected of being involved by a malignant process. One of the most important predictive and prognostic factors of a malignant lesion is whether the margins of the resected specimen are involved by the tumor or not. The purpose of this review is to provide an insight into grossing of a skin biopsy specimen with emphasis on techniques and reporting of excision biopsy margins.     

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.     

Multiarticular Tophaceous Gout with Severe Joint Destruction: A Pictorial Overview with a Twist

Tophi are the visible dermatological signs of gout. A case of tophaceous gout in a middle-aged man with no other metabolic derangement is being presented with multiple tophi on the hands and feet overlying joints as well as on the fingers and toes. We thought it to be of educational value to demonstrate needle-like crystals of urate by polarizing microscopy. X-rays of hands and feet showed dramatic destructive changes. The patient presented with mottled hypopigmentation on anterior and posterior knees and dorsa of hands and feet where he applied hot “aankda” leaves and covered them with bandage resulting in irritant dermatitis with postinflammatory hypopigmentation. This proved to be a red herring in this case.     

Plasma Levels of Interleukin-17, Interleukin-23, and Transforming Growth Factor-β in Sudanese Patients with Vitiligo: A Case-Control Study

Background:

Vitiligo is the most common pigmentary skin disorder. It is a multifactorial polygenic disease with epidermal melanocyte destruction. The cytokines profile found in vitiliginous patients was not fully elucidated.

Aims:

We sought to assess the autoimmune nature of vitiligo by comparing plasma levels of interleukin (IL)-17, IL-23, and transforming growth factor beta (TGF-β) in adult Sudanese vitiligo patients with matched control individuals.

Subjects and Methods:

Case-control study was conducted in Khartoum Dermatologic Teaching Hospital, in the period between July and December 2013. The cases were 42 adult Sudanese vitiligo patients matched with 43 control individuals. The cytokines were measured in the plasma by the quantitative “sandwich” ELISA.

Results:

Patients showed a significant lower median (25–75^th inter-quartile) of TGF-β than control (0.042 [0.041–0.044] vs. 0.047 [0.042–0.049]; P ≤ 0.001). Both IL-17 and IL-23 showed no significant difference between cases and controls. IL-17 showed a significant inverse relationship when correlated with TGF-β (r = −0.24; P = 0.026) while showing direct relationship when correlated with age (r = 0.28; P = 0.009).

Conclusion:

The positive findings detected in this study coincide with the important immunoregulatory role of the TGF-β, and support the autoimmune nature of the disease.     

Methodology Series Module 4: Clinical Trials

In a clinical trial, study participants are (usually) divided into two groups. One group is then given the intervention and the other group is not given the intervention (or may be given some existing standard of care). We compare the outcomes in these groups and assess the role of intervention. Some of the trial designs are (1) parallel study design, (2) cross-over design, (3) factorial design, and (4) withdrawal group design. The trials can also be classified according to the stage of the trial (Phase I, II, III, and IV) or the nature of the trial (efficacy vs. effectiveness trials, superiority vs. equivalence trials). Randomization is one of the procedures by which we allocate different interventions to the groups. It ensures that all the included participants have a specified probability of being allocated to either of the groups in the intervention study. If participants and the investigator know about the allocation of the intervention, then it is called an “open trial.” However, many of the trials are not open – they are blinded. Blinding is useful to minimize bias in clinical trials. The researcher should familiarize themselves with the CONSORT statement and the appropriate Clinical Trials Registry of India.     

Methodology Series Module 6: Systematic Reviews and Meta-analysis

Systematic reviews and meta-analysis have become an important of biomedical literature, and they provide the “highest level of evidence” for various clinical questions. There are a lot of studies – sometimes with contradictory conclusions – on a particular topic in literature. Hence, as a clinician, which results will you believe? What will you tell your patient? Which drug is better? A systematic review or a meta-analysis may help us answer these questions. In addition, it may also help us understand the quality of the articles in literature or the type of studies that have been conducted and published (example, randomized trials or observational studies). The first step it to identify a research question for systematic review or meta-analysis. The next step is to identify the articles that will be included in the study. This will be done by searching various databases; it is important that the researcher should search for articles in more than one database. It will also be useful to form a group of researchers and statisticians that have expertise in conducting systematic reviews and meta-analysis before initiating them. We strongly encourage the readers to register their proposed review/meta-analysis with PROSPERO. Finally, these studies should be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis checklist.     

Prevalence of Skin Changes in Diabetes Mellitus and its Correlation with Internal Diseases: A Single Center Observational Study

Background and Aim:

This single-center observational cross-sectional study has been done in an attempt to find out the prevalence of various skin manifestations in diabetes patients (DM) and their correlation with diabetes control and complications.

Materials and Methods:

Skin manifestations present over 12 months among those attend diabetes clinic were included in the study. Apart from demographic data and type, patients were also screened for micro vascular complications and control of diabetes over last 3 months.

Results and Discussion:

Sixty (n = 60) diabetes patisents (Type 1 DM, 9 patients and Type 2 DM 51 patients) have been found to have various skin lesions. Thirty-one (51.67%) patients presented with infectious conditions, vascular complications were present in 21 (35%) and dermatomes belonging to the miscellaneous group were present in 50 (83.33%) patients. Pyoderma, diabetic dermopathy, and pruritus without skin lesions were found to be most common manifestations in infective, vascular and miscellaneous group, respectively. Higher level of HB1_AC was found in patient with diabetic bulla (10.5 ± 0), scleredema (9.75 ± 0.77), lichen planus (9.3 ± 1.6), and acanthosis nigricans (9.15 ± 0.89). Patients with psoriasis and vitiligo had statistically significant lower level of glycosylated hemoglobin (P =< 0.001 and 0.03, respectively). However, no association of any kind of skin manifestation with DM with other microangiopathic complications was found in this study.     

Extrinsic apoptotic pathways: a new potential "target" for more sufficient therapy in a case of cutaneous anaplastic large cd30+ alk-T-cell lymphoma

The primary cutaneous T-cell lymphomas (CTCL) represent a clonal T-lymphocyte proliferation infiltrating the skin. CD30⁺T-cell lymphomas present clinically as nodules with a diameter between 1 and 15 cm, mostly in elderly patients. The role of the CD30 molecule in patients suffering from T-cell lymphomas is not completely clear yet. The signal transduction pathway which includes CD30 seems to play a key role in tumor progression. In certain forms of T-cellular lymphomas, the interaction between CD30/CD30-ligand is able to provoke apoptosis of the “tumor lymphocytes”. The modern conceptions of the pathogenesis of T-cell lymphomas include disorders in the pathways involved in programmed cellular death and disregulation in the expression of certain of its regulatory molecules. We are presenting an unusual case of a female patient with a primary cutaneous form of CD30⁺/ALK⁻ anaplastic large T-cell lymphoma. Upon the introduction of systemic PUVA, (psoralen plus ultraviolet light radiation) combined with beam therapy, a complete remission could be noticed. Eight months later, we observed a local recurrence, which was overcome by CHOP chemotherapy (Cyclophosphamide, Hydroxydaunorubicin (Doxorubicin), Vincristin (Oncovin®), Predniso(lo)n). Six months later, new cutaneous lesions had been noticed again. A new therapeutic hope for the patients with anaplastic large CTCL is actually based on the influence of the activity of the different apoptotic pathways. Death ligands, including tumor necrosis factor (TNF)-α, CD95L/FasL, and TRAIL, mediate also some important safeguard mechanisms against tumor growth in patients with CD30⁺ cutaneous anaplastic large T-cell lymphomas and critically contribute to lymphocyte homeostasis.     

Cowden Syndrome: Case Report,Update and Proposed Diagnostic and Surveillance Routines

Cowden syndrome (CS) is an infrequent autosomal dominant multisystem genodermatosis, generally involving the skin, oral mucosa, thyroid, breast and gastrointestinal tract. It is characterized by a late onset in the 2^nd or 3^rd decade of life, an extraordinary potential for malignant transformation, especially of breast and thyroid, and an identifiable germline mutation. In 80% cases, the human tumor suppressor gene, phosphatase and tensin homolog (PTEN) is mutated; mutations involving KILLIN, SDH B/D, PIK3CA and AKT1 genes account for the rest of the cases. Its clinical signs are not only the “essential pearls” for early and accurate diagnosis of CS but also help timely detection of neoplasia as they precede development of cancer by several years. We describe the first Indian and the third world report of polydactyly with CS, review this entity highlighting on recent clinical developments and emphasize on regular and thorough screening for prompt identification and management of the potentially malignant growths. We have also designed a baseline workup routine as well as a detailed screening program for these patients.