Lucio phenomenon mimicking antiphospholipid syndrome: The occurrence of antiphospholipid antibodies in a leprosy patient.

Lucio phenomenon is an atypical reaction of leprosy, characterized by vasculitic lesions that can mimic antiphospholipid syndrome (APS) clinically. Distinguishing the two can be difficult as antiphospholipid autoantibodies may be present in patients with leprosy. We report on a 32-year-old female patient presenting with a sudden onset of fever, hemorrhagic bullae, and skin necrosis on her lower legs. She was treated for APS due to the presence of antiphospholipid antibodies but had an inadequate response. A skin biopsy revealed thrombotic vasculopathy and necrotizing vasculitis associated with aggregation of foam cells in the perivascular area and subcutis, with acid-fast bacilli in the histiocytes and blood vessel walls. Direct immunofluorescence showed IgM, C3, and fibrinogen deposition in the superficial and deep dermal blood vessels. The pathology confirmed the diagnosis of Lucio phenomenon, and appropriate therapy was given. It is essential to evaluate the patient comprehensively, including clinical, serological, and pathological aspects, to obtain the correct diagnosis.

Immunohistochemical characterization of the M4 macrophage population in leprosy skin lesions.

BACKGROUND: Since macrophages are one of the major cell types involved in the Mycobacterium leprae immune response, roles of the M1 and M2 macrophage subpopulations have been well defined. However, the role of M4 macrophages in leprosy or other infectious diseases caused by mycobacteria has not yet been clearly characterized. This study aimed to investigate the presence and potential role of M4 macrophages in the immunopathology of leprosy. METHODS: We analyzed the presence of M4 macrophage markers (CD68, MRP8, MMP7, IL-6, and TNF-α) in 33 leprosy skin lesion samples from 18 patients with tuberculoid leprosy and 15 with lepromatous leprosy by immunohistochemistry. RESULTS: The M4 phenotype was more strongly expressed in patients with the lepromatous form of the disease, indicating that this subpopulation is less effective in the elimination of the bacillus and consequently is associated with the evolution to one of the multibacillary clinical forms of infection. CONCLUSION: M4 macrophages are one of the cell types involved in the microbial response to M. leprae and probably are less effective in controlling bacillus replication, contributing to the evolution to the lepromatous form of the disease.

N-acetylcysteine in dermatology.

N-acetylcysteine is a mucolytic drug which is commonly used as an antidote for acetaminophen toxicity. It is a thiol compound, which acts as a donor of cysteine, leading to replenishment of glutathione and thus acts as an antioxidant. It also has anti-inflammatory effects, alters the levels of neurotransmitters, inhibits proliferation of fibroblasts and keratinocytes and causes vasodilatation. Due to these actions, n-acetylcysteine has found use in several dermatologic conditions in systemic and topical form. The drug has been used as an adjuvant in the management of conditions such as toxic epidermal necrolysis, drug hypersensitivity syndrome, trichotillomania, skin picking disorders and onychotillomania, ichthyoses, contact dermatitis, atopic dermatitis, melasma, pseudoporphyria, connective tissue diseases, wound healing and alopecia. It also has a role in protection from radiation-induced skin damage including photo-ageing, photocarcinogenesis and radiation dermatitis. Most indications in dermatology are supported by case reports, small case series and small trials. Higher quality of evidence is needed for its wider use. The drug is cheap and is generally safe with few adverse effects. Thus a greater role is possible for use of n-acetylcysteine in various skin conditions. This review explores the various uses of n-acetylcysteine in the field of dermatology, the evidence supporting the same, the possible mechanisms of action and the adverse effects of the drug.

Mast cell heterogeneity and anti-inflammatory annexin A1 expression in leprosy skin lesions.

Mast cells (MCs) have important immunoregulatory roles in skin inflammation. Annexin A1 (ANXA1) is an endogenous anti-inflammatory protein that can be expressed by mast cells, neutrophils, eosinophils, monocytes, epithelial and T cells. This study investigated MCs heterogeneity and ANXA1 expression in human dermatoses with special emphasis in leprosy. Sixty one skin biopsies from 2 groups were investigated: 40 newly diagnosed untreated leprosy patients (18 reaction-free, 11 type 1 reaction/T1R, 11 type 2 reaction/T2R); 21 patients with other dermatoses. Tryptase/try+ and chymase/chy + phenotypic markers and toluidine blue stained intact/degranulated MC counts/mm2 were evaluated. Try+/chy+ MCs and ANXA1 were identified by streptavidin-biotin-peroxidase immunostaining and density was reported. In leprosy, degranulated MCs outnumbered intact ones regardless of the leprosy form (from tuberculoid/TT to lepromatous/LL), leprosy reactions (reactional/reaction-free) and type of reaction (T1R/T2R). Compared to other dermatoses, leprosy skin lesions showed lower numbers of degranulated and intact MCs. Try+ MCs outnumbered chy+ in leprosy lesions (reaction-free/reactional, particularly in T2R), but not in other dermatoses. Compared to other dermatoses, ANXA1 expression, which is also expressed in mast cells, was higher in the epidermis of leprosy skin lesions, independently of reactional episode. In leprosy, higher MC degranulation and differential expression of try+/chy+ subsets independent of leprosy type and reaction suggest that the Mycobacterium leprae infection itself dictates the inflammatory MCs activation in skin lesions. Higher expression of ANXA1 in leprosy suggests its potential anti-inflammatory role to maintain homeostasis preventing tissue and nerve damage.

Autophagy: A brief overview in perspective of dermatology.

Autophagy, literally meaning "self-eating," is an intracellular catabolic process of delivering cytosol and/or its specific content to the lysosomes for degradation.The resulting macromolecular constituents are recycled and utilized again by the cells. Basal level autophagy plays an important role in cellular homeostasis through the elimination of the old or damaged organelles, as well as aggregated intracellular proteins. Autophagy refers to sequestration of intact organelles along with a portion of cytosol, into a double-or multi-membrane structure known as phagophore, which elongates, and after closure, forms a vesicular structure known as the autophagosome. Subsequently, the mature autophagosome fuses with a lysosome, thereby forming a single membrane structure, an autolysosome. Autophagy plays a critical role in inflammation, autoimmunity and cellular differentiation. Skin serves as the first line of defense against a variety of environmental insults and autophagy is thought to be a form of an endogenous defense mechanism against such environmental derangements. Autophagy has been linked with keratinocyte differentiation and melanocyte survival, as well as with the pathogenesis of diverse skin disorders including systemic lupus erythematosus, systemic sclerosis, psoriasis, vitiligo, infectious skin diseases and cancer. Autophagy has been one of the most studied phenomena in cell biology and pathophysiology, and given its broad clinical implications, has become a major target for drug discovery. The last decade has seen a substantial upsurge in autophagy-related research and publications; still, the dermatology literature appears to be less initiated. Autophagy will probably change our understanding of dermatological disorders/medicines. Hence, a basic knowledge of autophagy is a prerequisite to understand the developments in the field of autophagy-related research.

Enfermedad de Hansen y ginecomastia / No disponible

La lepra es una de las causas de ginecotelia, sin embargo poco se ha publicado sobre este signo común y generalmente ignorado. La prevalencia de ginecomastia, una complicación bien conocida de la lepra en pacientes varones adultos, es poco reportada. El tratamiento temprano tiene un efecto notable en la reducción de la misma. Presentamos el caso de un varón con lepra multibacilar con ginecotelia y ginecomastia, en el curso de la enfermedad

Leprosy is one of the causes of gynaecothelia, however little has been published on this common and generally ignored sign. The prevalence of gynecomastia, a well known leprosy complication in adult male patients, is little reported. Early treatment has a marked effect in reducing it. Here we present the case of a man with multibacillary leprosy who had been associated gynaecothelia and gynecomastia in the course of the disease

Understanding itch: an update on mediators and mechanisms of pruritus.

Pruritus is the most common symptom secondary to skin diseases. Advances in the fields of neurobiology, immunology and physiology have made it possible for us to understand and unravel the deeper pathophysiological basis of pruritus. This review aims to update our current understanding of the mechanisms and mediators of pruritus. Special attention is paid to endogenous itch mediators particularly newly identified ones like endovanilloids, opioids, neurotrophins, cannabinoids, proteases and cytokines. Various theories explaining the peripheral encoding of itch are reviewed. Multiple neural pathways including the central itch pathways as well as supraspinal processing of itch and brain areas involved in pruritus are highlighted. Apart from peripheral itch mediators, spinal neural receptors are also involved in control of itch and should form part of the development of a novel antipruritic strategy. Further studies are required to fill the lacunae in our current understanding of the pathophysiology of pruritus.

Mechanobiological dysregulation of the epidermis and dermis in skin disorders and in degeneration.

During growth and development, the skin expands to cover the growing skeleton and soft tissues by constantly responding to the intrinsic forces of underlying skeletal growth as well as to the extrinsic mechanical forces from body movements and external supports. Mechanical forces can be perceived by two types of skin receptors: (1) cellular mechanoreceptors/mechanosensors, such as the cytoskeleton, cell adhesion molecules and mechanosensitive (MS) ion channels, and (2) sensory nerve fibres that produce the somatic sensation of mechanical force. Skin disorders in which there is an abnormality of collagen [e.g. Ehlers-Danlos syndrome (EDS)] or elastic (e.g. cutis laxa) fibres or a malfunction of cutaneous nerve fibres (e.g. neurofibroma, leprosy and diabetes mellitus) are also characterized to some extent by deficiencies in mechanobiological processes. Recent studies have shown that mechanotransduction is crucial for skin development, especially hemidesmosome maturation, which implies that the pathogenesis of skin disorders such as bullous pemphigoid is related to skin mechanobiology. Similarly, autoimmune diseases, including scleroderma and mixed connective tissue disease, and pathological scarring in the form of keloids and hypertrophic scars would seem to be clearly associated with the mechanobiological dysfunction of the skin. Finally, skin ageing can also be considered as a degenerative process associated with mechanobiological dysfunction. Clinically, a therapeutic strategy involving mechanoreceptors or MS nociceptor inhibition or acceleration together with a reduction or augmentation in the relevant mechanical forces is likely to be successful. The development of novel approaches such as these will allow the treatment of a broad range of cutaneous diseases.

The role of toll-like receptors in host defenses and their relevance to dermatologic diseases.

The family of toll-like receptors (TLRs) plays a central role in the cutaneous immune defense system. To date, different TLRs have been found on several major cell populations of the skin, such as keratinocytes, fibroblasts, antigen-presenting cells, and melanocytes. Activation of TLRs leads, via different intracellular signaling pathways, to the production of pro-inflammatory stimuli, and is considered a danger signal that should transform the skin in to the functional state of defense. However, TLRs have also been implicated in tissue homeostasis and renewal. Within the group of TLRs, two types have been identified: surface-expressed TLRs, which are predominantly active against bacterial cell wall compounds; and intracellular receptors, which preferentially recognize virus-associated pattern molecules. In addition, surface-expressed receptors trigger phagocytotic and maturation signals, while the intracellular TLRs lead to the induction of antiviral genes. Our review aims to outline the importance of TLRs in the pathogenesis of numerous skin diseases and the potential of TLR agonists as a treatment option for various skin diseases.

Arsenicosis: diagnosis and treatment.

Diagnosis of arsenicosis relies on both clinical and laboratory criteria, but principally it can be diagnosed on the basis of its cutaneous manifestations. Cutaneous manifestations (melanosis, keratosis, and cutaneous cancers) are essential clues in the diagnosis, and trained dermatologists or arsenic experts are able to clinically confirm a case even without laboratory backup. Although systemic manifestations are not considered as diagnostic hallmarks, yet their presence serves as important telltale signs in arriving at the diagnosis. In countries where laboratory facilities are available, measuring the level of arsenic in drinking water (consumed in the last 6 months), urine, hair, and nails is of immense value. Newer biomarkers of arsenic exposure are being explored to provide early information about arsenic intoxication, of which urinary porphyrin level, blood metallothionein have shown promising results. Controlling the problem of arsenicosis depends on various factors, of which the most important is cessation of intake of arsenic-contaminated water. Deep wells, traditional dug wells, treatment of surface water, rainwater harvesting, and removing arsenic from the contaminated water by arsenic removal plant or arsenic treatment unit are the available options for providing arsenic-free drinking water. The role of nutrition and antioxidants in preventing the onset of symptoms of arsenicosis is also of importance. Nonspecific therapies (e.g., keratolytics for hyperkeratosis) cannot also be ignored and serve as palliative measures. The persons affected need to be followed up at regular intervals to detect the onset of cancers (if any) at the earliest. Role of counseling and education should never be underestimated since absence of public awareness can undermine all efforts of mitigation measures.

S-100 as a useful auxiliary diagnostic aid in tuberculoid leprosy.

BACKGROUND: The diagnosis of tuberculoid leprosy is often difficult on hematoxylin and eosin (H&E) due to the absence of demonstrable nerve destruction. This study evaluates the utility of S-100 staining in identifying nerve fragmentation and differentiation of tuberculoid leprosy from other cutaneous granulomatous diseases. METHODS: Fifty cases of leprosy including 38 borderline tuberculoid (BT), two tuberculoid (TT), and 10 indeterminate leprosy (IL) were studied. Eleven controls of non-lepromatous cutaneous granulomatous lesions were included. S-100 was used for identifying the following dermal nerve patterns: infiltrated (A), fragmented (B), absent (C), and intact (D) nerves. RESULTS: On H&E, only 18/38 (47.4%) BT cases and 1/2 (50%) TT cases revealed neural inflammation. On S-100 staining of BT cases, 28/38 (73.7%) showed pattern B followed by patterns C and A in 8/38 (21.1%) and 2/38 (5.3%) cases, respectively. Both the TT cases showed pattern B. Only intact nerves (D) were seen in all the control cases. S-100 identified nerve damage in 4/10 (40%) IL cases. The patterns A, B, and C had sensitivity, specificity, and positive and negative predictive values of 100% in diagnosing tuberculoid (BT + TT) leprosy. CONCLUSIONS: S-100 is superior to H&E in identifying nerve fragmentation (p < 0.01). It also aids the differential diagnosis of tuberculoid leprosy.

Primary involvement of penile skin in lepromatous leprosy.

Skin lesions in lepromatous leprosy (LL) are usually multiple and widespread. Though the lesion may occur anywhere on the skin, male genitalia is rarely involved. In all cases reported so far about penile lesions of LL, there were lesions on the other parts of the body also. In some of the cases scrotum was also involved. We report here a patient who presented himself with a single macular lesion of leprosy on the shaft of his penis diagnosed as a case of lepromatous leprosy on slit-skin smear and histopathological examinations.

Immunohistological analysis of in situ expression of mycobacterial antigens in skin lesions of leprosy patients across the histopathological spectrum. Association of Mycobacterial lipoarabinomannan (LAM) and Mycobacterium leprae phenolic glycolipid-I (PGL-I) with leprosy reactions.

The presence of mycobacterial antigens in leprosy skin lesions was studied by immunohistological methods using monoclonal antibodies (MAbs) to Mycobacterium leprae-specific phenolic glycolipid I (PGL-I) and to cross-reactive mycobacterial antigens of 36 kd, 65 kd, and lipoarabinomannan (LAM). The staining patterns with MAb to 36 kd and 65 kd were heterogeneous and were also seen in the lesions of other skin diseases. The in situ staining of PGL-I and LAM was seen only in leprosy. Both antigens were abundantly present in infiltrating macrophages in the lesions of untreated multibacillary (MB) patients, whereas only PGL-I was occasionally seen in scattered macrophages in untreated paucibacillary lesions. During treatment, clearance of PGL-I from granulomas in MB lesions occurred before that of LAM, although the former persisted in scattered macrophages in some treated patients. This persistence of PGL-I in the lesions paralleled high serum anti-PGL-I antibody titers but was not indicative for the presence of viable bacilli in the lesions. Interestingly, we also observed a differential expression pattern of PGL-I and LAM in the lesions of MB patients with reactions during the course of the disease as compared with those without reactions. In conclusion, the in situ expression pattern of PGL-I and LAM in MB patients may assist in early diagnosis of reactions versus relapse.