Skin pigmentation is an important human phenotypic trait whose regulation, in spite of recent advances, has not yet been fully understood. The pigment melanin is produced in melanosomes by melanocytes in a complex process called melanogenesis. The melanocyte interacts with endocrine, immune, inflammatory and central nervous systems, and its activity is also regulated by extrinsic factors such as ultraviolet radiation and drugs. We have carried out a review of the current understanding of intrinsic and extrinsic factors regulating skin pigmentation, the melanogenesis stages and related gene defects. We focused on melanocyte-keratinocyte interaction, activation of melanocortin type 1 receptor (MC1-R) by peptides (melanocyte-stimulating hormone and adrenocorticotropic hormone) resulting from proopiomelanocortin (POMC) cleavage, and mechanisms of ultraviolet-induced skin pigmentation. The identification and comprehension of the melanogenesis mechanism facilitate the understanding of the pathogenesis of pigmentation disorders and the development of potential therapeutic options.
We describe 5 cases of anti-tumor necrosis factor-alpha (anti-TNF-α) induced psoriasiform eruptions with severe scalp involvement inducing inflammatory alopecia and review the literature on this subject. All our 5 patients were provided topical therapy, with good results in only 1 case. The remaining 4 were provided systemic therapy (methotrexate ± cyclosporine): 3 concomitantly suspended the anti-TNF-α treatment (2 are currently clear/almost clear but 1 has so far only observed mild improvement) and 1 switched anti-TNF-α (recurrent flare-ups of the disease continue). So far, no patient has developed scarring alopecia. To our knowledge, a total of 15 cases of anti-TNF-α induced psoriatic alopecia have been described. Anti-TNF-α was discontinued in 9 of the 15 patients and systemic therapy was provided to 9 of the 15 patients. Nonetheless, 2 patients developed scarring alopecia. We conclude that in anti-TNF-α induced psoriasiform eruptions some patients may respond to topical treatment, however in cases of severe scalp involvement anti-TNF-α suspension and systemic treatment should be considered in order to avoid scarring alopecia.
Dermatological manifestations occurred in almost one-third of our population. Infections were the most common complication, but anti-TNF-induced psoriasiform lesions were the most common cause for anti-TNF therapy definitive discontinuation.
TB may still occur in those with negative testing, some of them probably representing new infections instead of reactivations. Three out of 25 patients had TB in spite of previously treated LTB, although, the outcome of TB was not worse than in the general population.
Background: Toxic epidermal necrolysis (TEN) is a rare, drug-induced disease characterized by epidermal detachment and mucosal involvement. After an acute period, potentially disabling cutaneous and ocular sequels may appear. Although long-term complications are not rare, only few outcome studies are published. Objective: To evaluate the incidence of dermatological and ophthalmological sequels following TEN, to describe its clinical aspects and correlation with acute involvement. Patients and Methods: Eight patients surviving to TEN were submitted to dermatological and ophthalmological observation ranging from 0.5 to 8 years after hospitalization. Cutaneous and ocular involvement, during the acute phase, was retrospectively analysed. Results: Dermatological sequels were observed in 6 patients (75%) corresponding to those with more extensive skin involvement in the acute phase. The most frequent complications were cutaneous dyschromia (62.5%) and nail dystrophies (37.5%). Six patients (75%) had ocular complications with tarsal conjunctiva keratinization in 5 (62.5%) and keratoconjunctivitis sicca in 4 of them (50%). Trichiasis, corneal neovascularization and symblepharon were observed in 1 case. There was no correlation between the severity of acute ocular involvement and long-term complications. Conclusion: Following TEN, most patients have dermatological and ophthalmological sequels that persist for several years.
Biological therapy has revolutionized moderate to severe psoriasis treatment. However, despite being more effective than conventional systemic treatments, some patients do not respond or lose response to biotechnological treatments or develop drug-antibodies, interfering with its safety and efficacy. There are also clinical forms of the disease and patient profiles for which is pending further scientific evidence for more sustained therapeutic interventions. The continuous and more detailed knowledge of psoriasis pathophysiology has allowed identifying new therapeutic targets, which is expected to help overcome the challenges of individualized psoriasis treatment.
Tumor necrosis factor alpha inhibitors (anti-TNF-α) completely revolutionized the treatment of inflammatory bowel disease (IBD). However, anti-TNF-α-induced cutaneous side effects have been increasingly reported in the literature. Particularly, psoriasis and the recently recognized psoriasiform lesions are of particular concern, as anti-TNF-α agents are also used in the treatment of psoriasis, seemingly reflecting an immunological paradox. The clinical management of these cutaneous lesions is particularly challenging, owing to the potential need of anti-TNF-α discontinuation and scarcity of other therapeutic options. Therefore, optimization of current topical and systemic therapies and incorporation of new therapeutic agents is of great interest. Our aim is to review data in the literature regarding the clinical management of these cutaneous lesions and provide a therapeutic algorithm, supported by our experience as a tertiary referral center for IBD. Although in older reports no distinction was made, anti-TNF-α-induced psoriasiform lesions are not only more prevalent but also bear notable differences from classical psoriasis, possibly reflecting a different nosological entity. Onset of lesions has been related to periods of IBD remission, as supported by low levels of fecal calprotectin. Psoriasiform lesions can be adequately managed either by topical (glucocorticoids, calcineurin inhibitors, and antibiotics) or systemic (phototherapy, acitretin, glucocorticoids, and antibiotics) therapies and/or switch to other anti-TNF-α agents. Data referring to patients who were able to continue on the same IBD therapy ranged from 30.7 to 100%, reinforcing the importance of an adequate control of these lesions. The recently approved ustekinumab offers another step in the management of anti-TNF-α-intolerant patients.
Restrictive dermopathy (RD) is a rare, fatal, and genetically heterogeneous laminopathy with a predominant autosomal recessive heredity pattern. The phenotype can be caused by mutations in either LMNA (primary laminopathy) or ZMPSTE24 (secondary laminopathy) genes but mostly by homozygous or compound heterozygous ZMPSTE24 mutations. Clinicopathologic findings are unique, allowing a specific diagnosis in most cases. We describe a premature newborn girl of non-consanguineous parents who presented a rigid, translucent and tightly adherent skin, dysmorphic facies, multiple joint contractures and radiological abnormalities. The overall clinical, radiological, histological, and ultrastructural features were typical of restrictive dermopathy. Molecular genetic analysis revealed a homozygous ZMPSTE24 mutation (c.1085_1086insT). Parents and sister were heterozygous asymptomatic carriers. We conclude that RD is a relatively easy and consistent clinical and pathological diagnosis. Despite recent advances in our understanding of RD, the pathogenetic mechanisms of the disease are not entirely clarified. Recognition of RD and molecular genetic diagnosis are important to define the prognosis of an affected child and for recommending genetic counseling to affected families. However, the outcome for a live born patient in the neonatal period is always fatal.
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