Livedoid vasculopathy in 75 Brazilian patients in a single-center institution: Clinical, histopathological and therapy evaluation.

This study presents a single center experience with livedoid vasculopathy (LV). A rare disease that can lead to severe quality of life impairment. Characterize clinical data of LV patients at the Dermatology Division at the University of São Paulo. A retrospective and transversal study was conducted, from 1 January 2005 to 31 December 2019. About 75 patients diagnosed as LV and confirmed by skin biopsy were included. Epidemiology, clinical appearance, histopathology data, and treatment history were observed. There were 78.66% Caucasian women, with a mean age of 39.9 years. Frequent cutaneous manifestations were ulcers, atrophic blanche-like scars, hyperpigmentation, purpuras, telangiectasias, and livedo racemosa. Pain, pruritus, and hypoesthesia were the main symptoms. After treatment, almost 40% of cases relapsed during spring and summer months. About 66% of cases had thrombophilia factors associated, such as high levels of lipoprotein(a). Frequent treatments included acetylsalicylic acid, pentoxifylline, and diosmin with hesperidin. Not being a prospective study. This research provides useful data on Latin American LV patients, indicating multifactorial conditions involved in LV pathogenesis. An extensive work-up including autoimmune laboratory tests, thrombophilia factors, and other conditions associated with venous stasis should be part of LV investigation and controlled to improve treatment response.

"Normal-appearing" scalp areas are also affected in lichen planopilaris and frontal fibrosing alopecia: An observational histopathologic study of 40 patients.

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocyte-mediated scarring alopecias which clinically affect primarily the anterior and mid-scalp. However, unaffected scalp areas have not yet been investigated in a systemic manner. In this study, we assessed histopathologic changes in affected and unaffected scalp in both diseases and healthy control subjects and compared these findings with clinical signs and scalp symptoms. We have demonstrated that "normal-appearing" scalp that is devoid of clinical lesions of LPP and FFA showed lymphocytic perifollicular inflammation around the isthmus/infundibulum areas in 65% of biopsy specimens, perifollicular fibrosis in 15% and mucin deposits in 7.5% of the cases. None of these findings were found in control samples. No direct correlation was found between the degree of histopathological inflammation, scalp symptoms and clinical lesions in the corresponding affected scalp areas. This preliminary study suggests that both diseases may be more generalized processes which affect the scalp and therefore need systemic or total scalp therapy.

Evidence for neurogenic inflammation in lichen planopilaris and frontal fibrosing alopecia pathogenic mechanism.

Lichen planopilaris (LPP) and frontal fibrosing alopecia (FFA) are lymphocytic scarring alopecias affecting primarily the scalp. Although both diseases may share some clinical and histopathological features, in the last decade, FFA has become an "epidemic" particularly in Europe, North and South America with unique clinical manifestations compared to LPP, thus, raising the idea that this disease may have a different pathogenesis. Symptoms such as scalp burning, pruritus or pain are usually present in both diseases, suggesting a possible role for nerves and neuropeptides in the pathogenesis of both diseases. Based on some previous studies, neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), have been associated with lipid metabolism and many chronic inflammatory disorders. In this study, we asked if these neuropeptides are associated with LPP and FFA scalp lesions. Alteration in the expression of SP and CGRP in affected and unaffected scalp skin from patients with both diseases was found with examination of sections using immunohistochemical techniques and confocal microscopy. We then quantitatively assessed and compared SP and CGRP expression from control, LPP and FFA scalp biopsies. Although LPP and FFA share similar histopathologic findings, opposite results were found in affected and unaffected scalp in the ELISA tests, suggesting that these diseases may have different pathogenic mechanisms. We also found presence of histopathological inflammation irrespective of evident clinical lesions, which raises the possibility that both diseases may be more generalized processes affecting the scalp.

Poikilodermatous Mycosis Fungoides: Comparative Study of Clinical, Histopathological and Immunohistochemical Features.

BACKGROUND: Poikilodermatous mycosis fungoides (pMF) is characterized by poikiloderma areas, typically involving the major flexural areas and trunk. Its presentation can be generalized or admixed with other forms of MF. Previous studies fail to correlate the clinical presentation with prognosis and laboratory findings. Some reports show pityriasis lichenoides chronica (PLC) preceding the poikiloderma. OBJECTIVES: Correlate prognostic, histopathological and molecular aspects of pMF with its clinical presentation. METHODS: Retrospective analysis of 14 cases of generalized pMF (GpMF), 22 of localized pMF (LpMF) and 17 of pMF admixed with other forms of MF (mix-pMF). RESULTS: Female predominance and lower age at diagnosis was found in all groups compared to classic MF, a high prevalence of PLC-like lesions in the GpMF group and a high rate of hypopigmented lesions in the mix-pMF group. There were 2 deaths within the GpMF group. Histology was similar to previously reported findings, as was the prevalence of CD4 T-cell infiltrate, compared to CD8. The T-cell clonality positivity was lower in the GpMF group, compared to other groups (27% GpMF, 80% LpMF and 100% mix-pMF). DISCUSSION: This is the first article to categorize the different forms of pMF and correlate them with clinical and laboratory findings. The dermatological presentation differs among the groups. There was a high frequency of PLC-like lesions within the GpMF group and of hypopigmented lesions in mix-pMF. The histological and immunohistochemical findings were similar to those previously reported. Aggressive treatments are not recommended due to the good prognosis of all pMF forms. The low positivity of T-cell clonality in the GpMF group should be investigated.

Ulcers in leprosy patients, an unrecognized clinical manifestation: a report of 8 cases.

BACKGROUND: Leprosy is a chronic granulomatous infection caused by Mycobacterium leprae. It is a polymorphic disease with a wide range of cutaneous and neural manifestations. Ulcer is not a common feature in leprosy patients, except during reactional states, Lucio's phenomenon (LP), or secondary to neuropathies. CASES PRESENTATION: We report eight patients with multibacillary leprosy who presented specific skin ulcers as part of their main leprosy manifestation. Ulcers were mostly present on lower limbs (eight patients), followed by the upper limbs (three patients), and the abdomen (one patient). Mean time from onset of skin ulcers to diagnosis of leprosy was 17.4 months: all patients were either misdiagnosed or had delayed diagnosis, with seven of them presenting grade 2 disability by the time of the diagnosis. Reactional states, LP or neuropathy as potential causes of ulcers were ruled out. Biopsy of the ulcer was available in seven patients: histopathology showed mild to moderate lympho-histiocytic infiltrate with vacuolized histiocytes and intact isolated and grouped acid-fast bacilli. Eosinophils, vasculitis, vasculopathy or signs of chronic venous insufficiency were not observed. Skin lesions improved rapidly after multidrug therapy, without any concomitant specific treatment for ulcers. CONCLUSIONS: This series of cases highlights the importance of recognizing ulcers as a specific cutaneous manifestation of leprosy, allowing diagnosis and treatment of the disease, and therefore avoiding development of disabilities and persistence of the transmission chain of M. leprae.

Viremia and viruria of trichodysplasia spinulosa-associated polyomavirus before the development of clinical disease in a kidney transplant recipient.

Trichodysplasia spinulosa (TS) is a rare disease associated with immunosuppression and induced by a polyomavirus denominated Tricodisplasia Polyomavirus (TSPyV). We report a case of TS 6 months after kidney transplantation in a 65 years-old woman under immunosuppression therapy with prednisone, mycophenolate and tacrolimus. The patient developed follicular papules on the face with a thickening of the skin and alopecia of the eyebrows, leading to distortion of the face and a leonine appearance characteristic of the disease. The skin biopsy confirmed the clinical diagnosis and the presence of TSPyV DNA in the skin was detected. Staining for SV40 was positive. Immunosuppression was changed: mycophenolate was withdrawn, tacrolimus reduced and everolimus added. Intravenous cidofovir and later on leflunomide were added. Although the literature has reported clinical success with topical cidofovir, we were unable to use it because this drug is not available. There was an improvement of skin lesions and on cosmetic appearance. The patient had three rejections (one clinically diagnosed and two other biopsy proven), progressed with renal failure and graft loss. Retrospective analysis of stored urine and blood samples detected TSPyV DNA in some of those samples two months before the TS clinical development. This case highlights the TSPyV detection in blood and urine samples before the development of skin lesions.

Histopathological and clinical evaluation of chronic spontaneous urticaria patients with neutrophilic and non-neutrophilic cutaneous infiltrate.

BACKGROUND: Chronic urticaria has an expressive prevalence in general population, especially in adults, and is defined by the presence of intermittent hives for six weeks or longer. Our study aims to characterize the histological patterns of chronic spontaneous urticaria, based on the inflammatory cell infiltrate, and correlate them to laboratory exams. METHODS: It was performed a retrospective analysis of laboratory, histopathology and direct immunofluorescence data of 93 patients with chronic urticaria. For histopathological analysis, cell count was performed in four fields at high magnification (×400) for each specimen. The resulting cell count medians were submitted to statistical analysis and, then, were correlated to laboratorial findings. RESULTS: We found a female predominance (76.34%) of chronic urticaria cases, and an average age of 42.5 years (SD ± 15). Two histological groups were distinctive: 1) chronic urticaria with predominance of neutrophils or eosinophils - N (%) = 39 (42.4%) - and 2) chronic urticaria with predominance of lymphocytes - N (%) = 53 (57.6%). There was not significant correlation between histological groups and laboratorial tests. Moreover, direct immunofluorescence was positive in 21 (33,87%) from 62 patients. CONCLUSIONS: There is not enough scientific evidence to support neutrophilic urticaria as a solid, separate entity.

Severe type 1 upgrading leprosy reaction in a renal transplant recipient: a paradoxical manifestation associated with deficiency of antigen-specific regulatory T-cells?

BACKGROUND: Due to its chronic subclinical course and large spectrum of manifestations, leprosy often represents a diagnostic challenge. Even with proper anti-mycobacteria treatment, leprosy follow up remains challenging: almost half of leprosy patients may develop reaction episodes. Leprosy is an infrequent complication of solid organ transplant recipients. This case report illustrates the challenges in diagnosing and managing leprosy and its reactional states in a transplant recipient. CASE PRESENTATION: A 53-year-old man presented 34 months after a successful renal transplantation a borderline-tuberculoid leprosy with signs of mild type 1 upgrading reaction (T1R). Cutaneous manifestations were atypical, and diagnosis was only made when granulomatous neuritis was found in a cutaneous biopsy. He was successfully treated with the WHO recommended multidrug therapy (MDT: rifampicin, dapsone and clofazimine). However he developed a severe T1R immediately after completion of the MDT but no signs of allograft rejection. T1R results from flare-ups of the host T-helper-1 cell-mediated immune response against Mycobacterium leprae antigens in patients with immunologically unstable, borderline forms of leprosy and has been considered an inflammatory syndrome in many aspects similar to the immune reconstitution inflammatory syndromes (IRS). The T1R was successfully treated by increasing the prednisone dose without modifying the other immunosuppressive drugs used for preventing allograft rejection. Immunological study revealed that the patient had a profound depletion of both in situ and circulating regulatory T-cells and lack of expansion of the Tregs upon M. leprae stimulation compared to T1R leprosy patients without iatrogenic immunosuppression. CONCLUSIONS: Our case report highlights that leprosy, especially in the transplant setting, requires a high degree of clinical suspicion and the contribution of histopathology. It also suggests that the development of upgrading inflammatory syndromes such as T1R can occur despite the sustained immunosuppressors regimen for preventing graft rejection. Our hypothesis is that the well-known deleterious effects of these immunosuppressors on pathogen-induced regulatory T-cells contributed to the immunedysregulation and development T1R.

Sweet Syndrome: Clinical Features, Histopathology, and Associations of 83 Cases.

BACKGROUND: Sweet syndrome (SS) is an infrequent skin disease characterised by sudden onset of fever, leukocytosis, neutrophilia, and tender erythematous plaques infiltrated by neutrophils. Multiple conditions have been associated with this syndrome. OBJECTIVES: The aim of this study was to evaluate the clinical, epidemiological, laboratory, and histopathological findings and associations of patients with SS. METHODS: We conducted a retrospective study of 83 patients with SS followed between January 1, 2006, and January 31, 2015. RESULTS: Of the patients, 82% were female; the mean age at onset was 48 years. Clinical presentation was mainly characterised by erythematous and edematous plaques, mostly on upper extremities and trunk. Fever was observed in 32%; 60% presented leukocytosis and 39% neutrophilia. On histopathological examination, neutrophilic and lymphohistiocytic infiltrate and edema were the most frequent findings. Fourteen percent of patients had malignancy or hematologic disorders, 26% were classified as having drug-induced SS, and 24% noted recent infection. Only 2 cases occurred during pregnancy. Systemic corticosteroid was the most common choice of treatment, with excellent response. In malignancy-associated SS, the mean hemoglobin level was lower ( P = .01) and the erythrocyte sedimentation rate (ESR) was higher ( P = .04) in comparison to classic and drug-induced SS. Leukocytoclasia was associated with higher risk of recurrence ( P = .01). CONCLUSION: All patients with SS deserve careful investigation of possible underlying conditions. Higher ESR and lower hemoglobin levels might reinforce the need of malignancy screening. Also, leukocytoclasia appears to be a potential marker of higher recurrence rate, demanding closer and longer follow-up.

Clinical and Histopathologic Assessment of Facial Melasma After Low-Fluence Q-Switched Neodymium-Doped Yttrium Aluminium Garnet Laser.

BACKGROUND: Melasma is a frequent and difficult to treat skin disorder. Results of laser therapy are inconsistent. OBJECTIVE: To determine the safety and efficacy of low-fluence Q-switched neodymium-doped yttrium aluminum garnet (QS Nd:YAG) laser for melasma treatment and assess recurrence rates and histopathologic findings before and after treatment. METHODS: Twenty patients were treated with 10 weekly sessions of low-fluence 1064-nm QS Nd:YAG laser at 1-week intervals. The modified Melasma Area and Severity Index (mMASI) score was evaluated at baseline; 1 week; and 1, 3, and 6 months after treatment. Epidermal melanin quantification was performed on 10 biopsy samples and compared before and after treatment. RESULTS: All patients showed improvement by mMASI scores, range (21%-75%) compared with that at baseline. No permanent side effects occurred. The recurrence rate was 81%. By histopathology, a slight, nonsignificant (p = .305) decrease in melanin deposition was seen in all layers of the epidermis 1 week after the laser treatments ended. CONCLUSION: The results confirm the safety and effectiveness of low-fluence QS Nd:YAG laser for treating melasma; however, the high recurrence suggests poor long-term results when the laser is used as a monotherapy.

Generalized lenticular atrophoderma of Pasini and Pierini.

We present a 16-year-old boy with multiple, well-circumscribed, atrophic, light-brown patches on his neck, chest, and back. The authors believe that it represents an unusual presentation of atrophoderma of Pasini and Pierini and suggest the designation "generalized lenticular APP."

[Not Available]. / Síndrome de Graham-Little-Piccardi-Lassueur: variante disseminada de líquen plano folicular.

Graham-Little-Piccardi-Lassueur syndrome is a rare lichenoid dermatosis. It is characterized by the triad of scarring alopecia of the scalp, alopecia of the axilla and or groin, and keratotic follicular papules of the body. The present paper reports on two cases affecting young women. Histopathological findings suggest the disorder represents a generalized form of lichen planus follicularis.

Topical application of imiquimod as a treatment for chromoblastomycosis.

Chromoblastomycosis is a subcutaneous mycosis that remains a therapeutic challenge, with no standard treatment and high rates of relapse. On the basis of our recent discoveries in mouse models, we tested the efficacy of topical applications of imiquimod to treat patients afflicted with this chronic fungal infection. We report results of treatment for the first 4 recipients of topical imiquimod, all of whom displayed a marked improvement of their lesions, both with and without concurrent oral antifungal therapy.

Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression.

BACKGROUND: Methotrexate (MTX) is an alternative treatment for patients with moderate/severe atopic dermatitis (AD). OBJECTIVE: The authors evaluated the effect of MTX on the cutaneous expression of cytokines and chemokines that are involved in the inflammatory response in adult AD patients who received treatment with methotrexate for 24 weeks. METHODS: The authors conducted a prospective single-institution cohort study with 12 adults with moderate/severe AD who received oral MTX (15 mg/wk for 24 wks) and 10 non-atopic matched controls. The comparison was made of skin biopsies of lesional and non-lesional skin, pre- and post MTX treatment. The authors analyzed mean epidermal thickness and expression of IL-31, IL-31RA, OSMR, TSLP, Ki67, IL-4 mRNA, IL-6, IL-10, TNF-α, IFN-γ, TARC, and CCL-22. RESULTS: There was a reduction in mean epidermal thickness (p = 0.021), an increase in IL-31RA expression (immunohistochemistry) in the epidermis (p = 0.016) and a decrease in IL-31 gene expression (p = 0.019) on lesional AD skin post-MTX treatment. No significant changes in the cutaneous expression of the other evaluated markers were identified. STUDY LIMITATIONS: Small sample size and limited length of follow-up. CONCLUSIONS: Treatment with MTX in adults with moderate/severe AD reduced epidermal hyperplasia and changed the cutaneous expression of inflammatory cytokines and receptors that are mainly related to pruritus, including IL-31 and IL-31RA. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03327116.

Sensitive Scalp and Trichodynia: Epidemiology, Etiopathogenesis, Diagnosis, and Management.

Sensitive scalp (SSc) is considered a sensitive skin on the scalp, with its particularities. Although it is not rare in the dermatological practice and the term is commonly present in personal care products, this entity is poorly investigated in the medical literature. The etiopathogenesis is still uncertain, and the sensitivity may be associated with hair loss. Clinical manifestations are subjective symptoms of pruritus, burning, pain, pricking, and/or trichodynia, often with scalp erythema. SSc can be triggered by several factors (endogenous or exogenous). The diagnosis is guided by the anamnesis, and there are still no specific trichoscopic features. Trigeminal trophic syndrome and postherpetic neuralgia are the main differential diagnosis to be considered. We organized the therapeutical approach in three steps: scalp care, topical and systemic treatment.

Efficacy and Safety of Scalp Microneedling in Male Pattern Hair Loss.

Introduction: There are few reports involving scalp microneedling in MPHL patients, and in most of them, physical stimulus is associated with other therapeutic agents. The aim of this study was to evaluate the efficacy and risks of isolated scalp microneedling in MPHL patients. Methods: Thirty patients were included in this randomized single-blinded study and submitted to 4 monthly scalp microneedling sessions. Two different microneedling devices were used: roller (n = 15) and tattoo cartridge (n = 15). Scalp coverage and hair density changes were measured 4 and 16 weeks after the last session. Adverse events were observed throughout the study, and scalp biopsies were performed before and after to investigate scarring changes. Results: Four of 12 participants in the roller group and 2 of 14 participants in the tattoo cartridge group showed an improvement in clinical pictures at the first follow-up visit. Only half of these patients sustained an improvement until the last follow-up visit. No benefit in hair density was observed in either group. No reports of adverse events were made. Neocollagenesis and elastolysis were noted in scalp biopsies. Discussion/Conclusion: Isolated scalp microneedling did not show improvement in scalp coverage or hair density of MPHL participants in this study.

Assessment of reflectance confocal microscopy for monitoring treatment of actinic keratosis and field cancerization with daylight photodynamic therapy.

Actinic keratosis (AK) is the most common pre-malignant cutaneous lesion of the skin, often associated with field cancerization. Daylight photodynamic therapy (DL-PDT) is used as treatment, showing good histological results. Reflectance confocal microscopy (RCM) may be useful as a non-invasive, real-time approach to monitor treatment, however, there is a lack of data on the correlation between RCM and histopathological findings in AK patients treated with DL-PDT. To correlate histological and RCM findings and evaluate the efficacy of DL-PDT in patients with AK and field cancerization treated with DL-PDT. Patients with field cancerization and a minimum of six AK lesions on the face were included in the study. A single session combining methyl aminolevulinate followed by two-hour daylight exposure of the face was performed. RCM and biopsy were performed before and after three months of the intervention to compare efficacy between patients using the Wilcoxon test, and concordance of the findings based on the different methods was analysed using the Kappa test. Twenty-four patients completed the study. An improvement in photodamage and a decrease in the number of AK lesions (45.3% reduction) was observed. Regression in atypia and dysplasia was observed via histopathology and RCM, however, there was poor agreement between the methods. No changes were observed after treatment for inflammation, fibroplasia and acantholysis. Concordance between histological and RCM findings was poor, suggesting that RCM cannot replace the histopathological examination, however, it may be used as an adjuvant test for follow-up of patients. Despite this, DL-PDT proved to be an effective method for treating AK.