Ricardo Romiti

Induction or exacerbation of psoriatic lesions during anti-TNF-α therapy for inflammatory bowel disease: A systematic literature review based on 222 cases ☆

BACKGROUND Paradoxical cases of psoriatic lesions induced or exacerbated by anti-tumor necrosis factor (TNF)-α therapy have been reported more frequently in recent years, but data related to inflammatory bowel disease (IBD) are rare. A systematic literature review was performed to provide information about this adverse effect in patients with IBD who receive anti-TNF therapy. METHODS Published studies were identified by a search of Medline, Embase, Cochrane, SciELO, and LILACS databases. RESULTS A total of 47 studies (222 patients) fulfilled the inclusion criteria and were selected for analysis. Clinical and therapeutic aspects varied considerably among these reports. Of the 222 patients, 78.38% were diagnosed with Crohns disease, and 48.20% were female. The mean patient age was 26.50 years, and 70.72% of patients had no history of psoriasis. Patients developed psoriasiform lesions (55.86%) more often than other types of psoriatic lesions, and infliximab was the anti-TNF-α therapy that caused the cutaneous reaction in most patients (69.37%). Complete remission of cutaneous lesions was observed in 63.96% of the cases. CONCLUSIONS We found that psoriatic lesions occurred predominantly in adult patients with Crohns disease who received infliximab and had no previous history of psoriasis. Most patients can be managed conservatively without discontinuing anti-TNF-α therapy.

Cutaneous lupus erythematosus: First multicenter database analysis of 1002 patients from the European Society of Cutaneous Lupus Erythematosus (EUSCLE)

In this prospective, cross-sectional, multicenter study, we assessed clinical and laboratory characteristics from patients with cutaneous lupus erythematosus (CLE) using the Core Set Questionnaire of the European Society of Cutaneous Lupus Erythematosus (EUSCLE). 1002 (768 females, 234 males) patients with different subtypes of CLE, such as acute CLE (ACLE, 304 patients), subacute CLE (SCLE, 236 patients), chronic CLE (CCLE, 397 patients), and intermittent CLE (ICLE, 65 patients), from 13 European countries were collected and statistically analyzed by an SPSS database. The main outcome measures included gender, age at onset of disease, LE-specific and LE-nonspecific skin lesions, photosensitivity, laboratory features, and the criteria of the American College of Rheumatology (ACR) for the classification of systemic lupus erythematosus. The mean age at onset of disease was 43.0±15.7 years and differed significantly between the CLE subtypes. In 347 (34.6%) of the 1002 patients, two or more CLE subtypes were diagnosed during the course of the disease and 453 (45.2%) presented with LE-nonspecific manifestations. Drug-induced CLE and Sjögrens Syndrome had the highest prevalence in SCLE patients (13.1% and 14.0%, respectively). Photosensitivity was significantly more frequent in patients with ACLE, SCLE, and ICLE compared with those with CCLE. The detection of antinuclear antibodies such as anti-Ro/SSA and anti-La/SSB antibodies revealed further significant differences between the CLE subtypes. In summary, the EUSCLE Core Set Questionnaire and its database facilitate the analysis of clinical and laboratory features in a high number of patients with CLE and will contribute to standardized assessment and monitoring of the disease in Europe.

Biopharmaceuticals and biosimilars in psoriasis: What the dermatologist needs to know

The entry of biosimilar forms of biopharmaceutical therapies for the treatment of psoriasis and other immune-mediated disorders has provoked considerable interest. Although dermatologists are accustomed to the use of a wide range of generic topical agents, recognition of key differences between original agent (ie, the name brand) and the generic or biosimilar agent is necessary to support optimal therapy management and patient care. In this review we have summarized the current state of the art related to the impending introduction of biosimilars into dermatology. Biosimilars represent important interventions that are less expensive and hence offer the potential to deliver benefit to large numbers of patients who may not currently be able to access these therapies. But the development of biosimilars is not equivalent to that of small molecule generic therapies because of differences in molecular structure and processes of manufacture. The planned regulatory guidelines and path to approval may not encompass all of these potentially important differences and this may have clinical relevance to the prescriber and patient. Consequently, we have identified a series of key issues that should be considered to support the full potential of biosimilars for the treatment of psoriasis; ie, that of increased access to appropriate therapy for the psoriasis population worldwide.

Localized scleroderma: clinical spectrum and therapeutic update.

Scleroderma is a rare connective tissue disease that is manifested by cutaneous sclerosis and variable systemic involvement. Two categories of scleroderma are known: systemic sclerosis, characterized by cutaneous sclerosis and visceral involvement, and localized scleroderma or morphea which classically presents benign and self-limited evolution and is confined to the skin and/or underlying tissues. Localized scleroderma is a rare disease of unknown etiology. Recent studies show that the localized form may affect internal organs and have variable morbidity. Treatment should be started very early, before complications occur due to the high morbidity of localized scleroderma. In this review, we report the most important aspects and particularities in the treatment of patients diagnosed with localized scleroderma.

Generalized Pustular Psoriasis in Childhood

Abstract:  Generalized pustular psoriasis is a rare form of psoriasis consisting of a generalized eruption of sudden onset with erythema and sterile pustules. In children, generalized pustular psoriasis is even more uncommon and may present as a severe and potentially life‐threatening disorder. In this study, we present demographics, clinical aspects, treatment response, and follow‐up of seven children with generalized pustular psoriasis. Retrospective study reviewing the records of seven children with generalized pustular psoriasis including age, gender, age of onset, presence of scalp and nail involvement, family history, concomitant diseases, precipitating factors, treatment modalities, and outcome. Age of first symptoms ranged from 1 month to 11 years. All patients received systemic retinoids at one time of the follow‐up period. Other treatment modalities included immunosuppressive drugs, biologics, phototherapy, and sulfasalazine. Two patients presented with severe constitutional illness, secondary infection and septic shock, including one fatal outcome. All further cases have remained free of recurrences for a mean period of up to 3 years. In our study, generalized pustular psoriasis presented a wide clinical spectrum in children ranging from mild, asymptomatic outbreaks to more severe, life‐threatening episodes. One fatality was observed. Children generally responded well to systemic retinoids. Further studies and long‐term follow‐up periods are needed to define potential trigger factors, efficacy and safety of different treatment modalities in children with generalized pustular psoriasis.

Infliximab, as sole or combined therapy, induces rapid clearing of erythrodermic psoriasis

but only HPV 72 was present in biopsies of the flat leucoplakic dysplastic lesions. This finding might indicate a particular preference of HPV 72 for the induction of oral mucosa dysplasias. Long-term follow-up of HIV-infected patients could provide more insights in the natural behaviour and clinical course of oral HPV infection. In general practice, screening programmes for HPV-related diseases in HIV-positive individuals should include both the anogenital area (using highresolution anoscopy) and the oral cavity (inspection with the naked eye).

Infliximab-induced psoriasis during therapy for Crohn's disease

Although therapy with tumor necrosis factor-alpha inhibitors (anti-TNF) provides beneficial effects in different immune inflammatory disorders, paradoxical cases of anti-TNF-induced psoriasis have increasingly been reported, mostly in the setting of rheumatologic diseases. To date, less than 50 cases of infliximab-induced psoriasis in inflammatory bowel disease patients have been described. The present report was aimed at describing two new cases of infliximab-induced psoriasis during therapy for Crohns disease and at carrying out a review on this intriguing phenomenon.

Childhood-onset bullous systemic lupus erythematosus.

Bullous systemic lupus erythematosus has rarely been described in pediatric lupus population and the real prevalence of childhood-onset bullous systemic lupus erythematosus has not been reported. From January 1983 to November 2013, 303 childhood-onset SLE (c-SLE) patients were followed at the Pediatric Rheumatology Unit of the Childreńs Institute of Hospital das Clínicas da Faculdade de Medicina Universidade da Universidade de São Paulo, three of them (1%) diagnosed as childhood-onset bullous systemic lupus erythematosus. All three cases presented tense vesiculobullous lesions unassociated with lupus erythematosus lesions, with the median duration of 60 days (30–60). All patients fulfilled bullous systemic lupus erythematosus criteria. Two had nephritis and serositis and presented specific autoantibodies. The histological pattern demonstrated subepidermal blisters with neutrophils-predominant infiltrates within the upper dermis. Direct immunofluorescence (DIF) showed deposits of IgG and complement along the epidermal basement membrane, in the presence or absence of IgA and/or IgM. A positive indirect immunofluorescence on salt-split skin demonstrating dermal binding was observed in two cases. All of them had moderate/severe disease activity at diagnosis with median Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) of 18 (14–24). Two patients received dapsone and one with severe nephritis received immunosuppressive drugs. In conclusion, in the last 30 years the prevalence of bullous lupus in childhood-onset lupus population was low (1%) in our tertiary University Hospital. A diagnosis of SLE should always be considered in children with recurrent tense vesiculobullous lesions with or without systemic manifestations.

Psoríase na infância e na adolescência

Psoriasis is a chronic, immunologically mediated, recurrent and universal inflammatory disorder. Approximately one third of adults refer onset before 16 years of age. The sooner the onset, the worse is the prognosis. In children, lesions may be physically disfiguring, leading to psychological impairment and evident loss of quality of life. Systemic therapy used in psoriasis, as well as phototherapy, has limited use in children due to accumulative effects of drugs, low acceptance, and risk of teratogenicity. In this section, we discuss the main clinical aspects of psoriasis in childhood and adolescence, differential diagnosis, therapeutic options, and prognosis.

Clinical and dermoscopic features of lichen planus pigmentosus in 37 patients with frontal fibrosing alopecia.

DEAR EDITOR, The coexistence of frontal fibrosing alopecia (FFA) and lichen planus pigmentosus (LPPigm), an uncommon macular variant of lichen planus, was first reported by Dlova in 2013 in South African patients. Herein, we report 37 patients with such an association, describe the clinical and dermoscopic features of facial LPPigm and compare our findings with previously published data. In total, 37 patients aged 34–79 years were included [36 women (30 postmenopausal, six premenopausal) and one man]; 33 had skin phototype IV or higher (hispanics and people of African descent) and three had skin phototype III. All patients presented with frontotemporal hair loss; three (8%) had the recently described pseudo ‘fringe sign’. Facial papules were noted in 16 (43%), eyebrow involvement in 36 (97%) and body hair loss in 27 (73%). All patients presented with facial hyperpigmentation, which we classified as diffuse in 25 (67%), reticulated in eight (22%) and comprised of multiple pigmented macules in four (11%) (Fig. 1a–c). In 14 (38%), neck involvement was also prominent. In 19 patients, LPPigm preceded FFA presentation, in five it followed diagnosis of FFA, in one patient FFA and LPPigm were diagnosed simultaneously and in 12 patients precise disease onset was unable to be confirmed. Punch biopsies were performed in 14 patients, confirming a clinical diagnosis of LPPigm, which showed an interface dermatitis pattern and/or pigment incontinence, occasionally involving hair follicles and eccrine glands (Fig. 1d–f). Epidermal atrophy and discrete perivascular lymphocytic infiltrate were commonly observed. Dermoscopy and photographic documentation of facial lesions were performed in all cases using either Fotofinder Dermoscope (nonpolarized; Teachscreen Software, Bad Birnbach, Germany), Fotofinder Handyscope (Teachscreen Software) or DermLite Foto II Pro (3Gen, San Juan Capistrano, CA, U.S.A.) attached to a Canon EOS T3i camera (polarized; Canon, Tokyo, Japan). The photographs were analysed by all authors and four distinct patterns of pigmentation were identified: (i) pseudonetwork (n = 24); (ii) dotted pattern (n = 8); (iii) speckled blue–grey dots (n = 13); and (iv) blue–grey dots arranged in circles (n = 7) (Fig. 1g–k), with 14 (38%) patients showing more then one pattern. Additionally, rhomboidal structures were noted in five patients with a pseudonetwork pattern and asymmetry of follicular openings in one (Fig. 1l, m). There was no correlation between the clinical type of pigmentation and one specific dermoscopic pigmentation pattern. Vascular alterations were assessed in 25 cases, and 12 presented focal erythema or telangiectasias and three diffuse erythema (Fig. 1g–i). Twenty-four patients presented complete or partial loss of facial vellus hair. In accordance with the initial description and later reports, coexistence of FFA and LPPigm in our series was observed mostly in dark-skinned patients (89%). Most of our patients were postmenopausal; only 17% were premenopausal. This differs from the series of Dlova, which included 64% premenopausal patients, but is similar to the recently published large series of patients with FFA. In the same study by Dlova, LPPigm preceded hair loss in all patients and was considered as a herald sign of FFA. A clear history of LPPigm preceding FFA was present in only 19 (51%) of our patients. However, considering that early signs of FFA and LPPigm can go unnoticed in patients, and a possible recall bias, we consider assessment of the predictive status of LPPigm as a harbinger of FFA to be hampered in the present study. The blue–grey hue observed through dermoscopy can be justified by the depth of the pigment present in the dermis, and has been described in lesions of lichen planus pigmentosus inversus. Speckled blue–grey dots and the pseudonetwork patterns possibly correlate with a more prominent interfollicular interface dermatitis; the former resulting from scattered foci of inflammation with melanophages, and the latter from a broader damage to the epidermal basal cell layer. Demonstration of eccrine and follicular involvement in biopsy specimens supports that the dotted pattern and circles result from damage to those structures, respectively. Blue–grey or brown perifollicular pigmentation in facial macules resembling LPPigm have been recently reported in patients with FFA and might correspond to the circles observed in our patients. Loss of facial vellus hairs also results from hair follicle involvement and has been previously described in FFA. Vascular changes might be found in the context of an inflammatory process and epidermal atrophy might have facilitated their visualization by dermoscopy. Clinically, the differential diagnosis of LPPigm should be established with a heterogeneous group of disorders causing facial hyperpigmentation, such as exogenous ochronosis, melasma, Riehl’s melanosis and ashy dermatosis. Hydroxychloroquine-induced hyperpigmentation should also be