Durability of the improvement of collagen I and collagen III with the use of oral isotretinoin in the treatment of photoaging.

BACKGROUND: Oral isotretinoin (ISO) is the drug of choice for the treatment of severe acne. For photoaging treatment, ISO has been proved to be effective in some controlled and noncontrolled trials and is an alternative to topical retinoic acid (RA) therapy, which causes an expected skin irritation. OBJECTIVE: To evaluate and compare the skin remodeling in patients taking ISO 20 mg 3 times a week for 12 weeks and 12 weeks after the end of the treatment to quantify collagen I and collagen III augmentation. MATERIAL AND METHODS: Immunohistochemical studies were performed to evaluate the expression of collagen I and collagen III, metalloproteinases (MMPs) -1, -3, -7, -9, -12, and the tissue inhibitor of MMP type-1 (TIMP-1) of the skin of 20 45 to 50-year-old women through morphometry in a semiquantitative method. The inclusion criteria were facial aging 2 and 3 of Glogau's classification, with phototypes between II and V who had not entered menopause. Biopsies of the skin of the left preauricular region were performed at three different times: pre-treatment (T0), end of 12-week treatment (T1), and 12 weeks posttreatment (T2). RESULTS: Collagen fibers I and III increased with statistical significance in T1 (50.7%; P = 0.012) but not in T2 (49.7%), which in turn was higher than in T0 (47.2%) for collagen I and T1 (33.3%; P = 0.002) but not in T2 (32.7%), and also was higher than T0 (32.0%) for collagen III. MMP-9 presented a decreased activity with statistical significance in T1 (P = 0.047) and T2 (P = 0.058). MMP-1 showed a reduction in T2 only (P = 0.015). MMPs -3, -7, -12, and TIMP-1 did not present significant modification in their expressions during or after the treatment. CONCLUSIONS: Low-dose ISO is effective in remodeling the extracellular matrix (ECM). This study found that the increase of collagen occurs through the augmentation of both collagen I and collagen III fibers. With originality, it was possible to verify the durability of these fibers for at least 12 weeks. This may be related to the decrease in MMP-9 expression verified at the end of the treatment and 12 weeks posttreatment.

Immunohistochemical detection of Treponema pallidum in skin samples with clinical and histopathological correlations and Warthin-Starry staining critical analysis

Abstract Background: Syphilis in its different phases may be a difficult diagnosis in clinical and histopathological grounds. Objectives: The present study objectives were to evaluate the detection and tissue distribution of Treponema pallidum in skin lesions of syphilis. Methods: A blinded diagnostic accuracy study was performed with immunohistochemistry and Warthin-Starry silver staining in skin samples from patients with syphilis and other diseases. Patients attended two tertiary hospitals between 2000 and 2019. Prevalence ratios (PR) and 95% confidence intervals (95% CI) were calculated for the association between immunohistochemistry positivity and clinical-histopathological variables. Results: Thirty-eight patients with syphilis and their 40 biopsy specimens were included in the study. Thirty-six skin samples were used as non-syphilis controls. The Warthin-Starry technique was unable to accurately demonstrate bacteria in all samples. Immunohistochemistry showed spirochetes only in skin samples from patients with syphilis (24/40) with 60% sensitivity (95% CI 44.8-75.2). Specificity was 100% and accuracy, 78.9% (95% CI 69.8-88.1). Most cases had spirochetes in both dermis and epidermis and there was a high bacterial load. Study limitations: Correlation between immunohistochemistry and clinical or histopathological characteristics was observed but was limited statistically due to the small sample size. Conclusions: Spirochetes were promptly seen in an immunohistochemistry protocol, which can contribute to the diagnosis of syphilis in skin biopsy samples. On the other hand, the Warthin-Starry technique showed to be of no practical value.

Immunohistochemical detection of Treponema pallidum in skin samples with clinical and histopathological correlations and Warthin-Starry staining critical analysis.

BACKGROUND: Syphilis in its different phases may be a difficult diagnosis in clinical and histopathological grounds. OBJECTIVES: The present study objectives were to evaluate the detection and tissue distribution of Treponema pallidum in skin lesions of syphilis. METHODS: A blinded diagnostic accuracy study was performed with immunohistochemistry and Warthin-Starry silver staining in skin samples from patients with syphilis and other diseases. Patients attended two tertiary hospitals between 2000 and 2019. Prevalence ratios (PR) and 95% confidence intervals (95% CI) were calculated for the association between immunohistochemistry positivity and clinical-histopathological variables. RESULTS: Thirty-eight patients with syphilis and their 40 biopsy specimens were included in the study. Thirty-six skin samples were used as non-syphilis controls. The Warthin-Starry technique was unable to accurately demonstrate bacteria in all samples. Immunohistochemistry showed spirochetes only in skin samples from patients with syphilis (24/40) with 60% sensitivity (95% CI 44.8‒75.2). Specificity was 100% and accuracy, 78.9% (95% CI 69.8‒88.1). Most cases had spirochetes in both dermis and epidermis and there was a high bacterial load. STUDY LIMITATIONS: Correlation between immunohistochemistry and clinical or histopathological characteristics was observed but was limited statistically due to the small sample size. CONCLUSIONS: Spirochetes were promptly seen in an immunohistochemistry protocol, which can contribute to the diagnosis of syphilis in skin biopsy samples. On the other hand, the Warthin-Starry technique showed to be of no practical value.

Cutaneous Horn of the Glans.

Cutaneous horn is a protuberance constituted by compact keratinous material, with a hard consistence similar to a horn, which occurs more frequently in photoexposed areas. The authors describe a case of cutaneous horn on the glans considered a rare location. Verrucous carcinoma was the histopathological diagnosis of the base of the horn and lichen sclerosis, the precursor lesion.

Paraneoplastic Dermatoses in Breast Cancer: Malignant Acanthosis Nigricans with Tripe Palm.

Our patient was a 43-year-old, single black woman, born and living in Paracambi, State of Rio de Janeiro, who worked as a surgical instrumentalist. She was sent to our sector of dermatology due to hypochromia and diffuse skin roughness that had first appeared 8 years previously. She had been diagnosed 6 months before admission with ductal infiltrating metastatic carcinoma in the right breast, with therapeutic failure of chemotherapy and radiotherapy. Her menarche had occurred at age 13 years, she reported normal menstrual cycles from there on, and she had never been pregnant. She denied neoplasias and other comorbidities in her family history.

Melanocytic lesions ≤ 6mm: Prospective series of 481 melanocytic trunk and limb lesions in Brazil.

Early diagnosis when melanoma is still small and thin is essential for improving mortality and morbidity. However, the diagnosis of small size melanoma might be particularly difficult, not only clinically but also dermoscopically. This study aimed to define clinical and dermatoscopic parameters in the diagnosis of suspicious pigmented cutaneous lesions with a diameter of ≤ 6mm and determine the sensitivity, specificity, positive and negative predictive values as well as the accuracy of each clinical and dermatoscopic criterion. This is a transversal, descriptive and analytical study of dermatoscopic analysis with the gold standard being the pathologic examination obtained from the excisional biopsy of suspicious melanocytic lesions with a diameter of ≤ 6mm. Trunk and limb lesion data from a public health service and a private clinic were prospectively collected from 2011 to 2017 by a unique observer. In total, 481 melanocytic lesions were included, with 73.8% being ≤ 4mm in diameter. Overall, 123 were diagnosed as melanoma, 56.0% in situ and 22.0% as thin melanomas (Breslow index 0.1 to 1.0mm). Melanoma presented symmetry in 53.7% of cases, regular borders in 54.5% and a single color in 60.2%. Regarding evolution, 13.8% of melanomas versus 10.9% of benign lesions (p = 0.116) were new by comparing photos from baseline with photos from the follow-up. The majority of melanomas (65%) were found on the limbs compared to 37.2% of the benign lesions at this location (p<0.001). A multiple logistic regression model adjusted for age, gender and location was created. The independent variables associated with the diagnosis of melanoma ≤ 6mm, adjusted for age, gender and location, were: streaks (adjusted Odds Ratio [aOR] 2.5; 95% CI 1.3-4.7; p = 0.006), and the presence of a structureless area (aOR 2.2, 95% CI 1.2-4.0, p = 0.011). Conversely, a symmetric typical pigment network was a protection variable (aOR 0.4, 95% 0.7-0.9, p = 0.040). In conclusion, dermatoscopic criteria have been identified which help to diagnose cases of small size melanoma. These include streaks and structureless areas that can be taken, particularly in consideration for the diagnosis of this subset of small difficult melanomas.

Validation of an algorithm based on clinical, histopathological and immunohistochemical data for the diagnosis of early-stage mycosis fungoides.

BACKGROUND: Diagnosis of mycosis fungoides is challenging due to the non-specificity of clinical and histopathological findings. The literature indicates an average delay of 4-6 years for a conclusive diagnosis. Refinement of the histopathological criteria for the diagnosis of patients in early stages of the disease is considered of interest. OBJECTIVES: To study the histopathological aspects of early-stage mycosis fungoides and the applicability, in a retrospective form, of the diagnostic algorithm proposed by Pimpinelli et al. METHODS: Observational, retrospective, transversal study based on revision of histopathological exams of patients with suspected mycosis fungoides. Medical records were reviewed, and complementary immunohistochemistry performed. RESULTS: Sixty-seven patients were included. The most frequent histopathological features were superficial perivascular lymphoid infiltrate (71.6%), epidermotropism (68.7%), lymphocytic atypia (63.8%), hyperkeratosis (62.7%) and acanthosis (62.7%). Forty-three patients scored 4 points at the algorithm, by clinical and histological evaluation. Immunohistochemistry was performed on 23 of the 24 patients with less than 4 points. Of those 23, 22 scored 1 point, allowing a total of 61 patients (91%) with the diagnosis of early-stage mycosis fungoides. STUDY LIMITATIONS: Its retrospective character, reduced sample size and incomplete application of the algorithm. CONCLUSIONS: Application of the Pimpinelli et al. algorithm, even in an incomplete form, increased the percentage of cases diagnosed as mycosis fungoides. Routine application of the algorithm may contribute to earlier and specific management and improvement of the patients' outcome.

Fractional Laser Resurfacing Treats Photoaging by Promoting Neocollegenesis and Cutaneous Edema.

BACKGROUND: Laser resurfacing is a common treatment for photoaging. This treatment creates skin incisions that initiate the wound healing cascade, including reorganization of the collagen matrix, in a dermal remodeling process that can last up to 12 months. OBJECTIVE: We compared the effects of nonablative and ablative Erbium fractional laser resurfacing on dermal content and arrangement of Collagen Types I and III, and on fibroblast activation. METHODS: Ten female patients (50-63 years) with Fitzpatrick Skin Types I-IV and clinical signs of photoaging underwent two types of Erbium fractional laser resurfacing (nonablative, 1540nm; ablative, 2940nm) on opposite sides of the face. Skin biopsies were obtained pretreatment and three months post-treatment. Morphometric analysis was performed using Picrosirius staining for overall collagen, and immunohistochemistry for Collagen Types I and III. Finally, hematoxylin and eosin staining was used to identify fibroblast activation. RESULTS: Both laser treatments induced reorganization of Collagen Types I and III and demonstrated signs of fibroblast activation. However, morphometric analysis of Picrosirius staining revealed that, after both treatments, there was a lower density of collagen fibers, which is characteristic of edema. CONCLUSION: At three months after laser resurfacing, skin lifting in photoaged skin likely resulted from new collagen deposition but also from edema.

Spiny keratoderma: Report of three cases.

BACKGROUND: Spiny keratoderma shows "music box spine" keratotic papules limited to the palms and soles and these lesions do not cause any trouble besides the cosmetic impairment and the sensation of roughness of hands and soles. AIM: To present cases and review the literature on spiny keratoderma. PATIENTS/METHODS, RESULTS: Three cases of spiny keratoderma are presented. The first case is a 52-year-old man with protein S deficiency presented with multiple spiny keratotic papules on palms and soles for more than 30 years, referring to remove them with a razor blade. The second case is an 84-year-old man who was hospitalized due to a rectal adenocarcinoma diagnosed 2 months before and presented multiples papules on palms and soles that were present for more than 50 years, with worsening after being bedridden. The third case is a 59-year-old woman who had since birth together with relatives the same type of spiny keratotic papules on palms and soles. CONCLUSION: The authors discuss the epidemiologic data and differential diagnosis of spiny keratoderma, as well as the related literature. Associations with systemic disease or malignancy occur in some acquired cases. It is important to distinguish from other palmoplantar keratodermas as some of that can be linked to cutaneous and internal malignancies. To date, no cases of spiny keratoderma in patients with protein S deficiency and only one case of association with rectal carcinoma have been reported.

Persistent Keratoses in Vitiligo.

The occurrence of keratoses in patients with psoriasis under treatment with psoralens and ultraviolet A (PUVA) has been described as an entity called PUVA keratosis. Similar lesions were seen later in patients with vitiligo under the same treatment. We describe the presence of distinct keratoses in the vitiligo lesions of three women patients from Rio de Janeiro, Brazil. The lesions started after PUVA treatment with total body irradiation, cabin or topical, and persisted long after the therapy was finished. All patients presented small rounded keratotic papules on achromic areas of the feet. Biopsies showed mild acanthosis, compact orthokeratotic hyperkeratosis, and hypergranulosis with increase of stratum granulosum layers or size increase of keratohyaline granules. Inflammatory infiltrate was sparse or absent. Cytologic atypia was not observed. Histologic features were compatible with reactive keratosis. None of the patients had a history of previous actinic keratosis or non-melanoma skin cancer and had been treated before with PUVA therapy either orally or topically; however, lesions occurred only in areas exposed to sunlight and persisted for long periods, even without treatment with PUVA or narrowband ultraviolet B (NB-UVB). The authors discuss whether these lesions can be considered as PUVA keratosis or if the sun exposure may have played an important role in the reported cases.

Evaluation of the Cutaneous Lymphoma International Prognostic Index in patients with early stage mycosis fungoides

Abstract: Background: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. TNMB system is the staging method used in MF, and it not only guides therapeutic management, but represents the main prognostic factor. In order to improve the prognostic evaluation, the Cutaneous Lymphoma International Prognostic Index (CLIPi) was proposed. Objective: To evaluate the performance of CLIPi score for prognostic analysis in patients with early stage MF. Methods: This is a retrospective cross-sectional observational study, with exploratory analysis. The outcome variables were disease progression and related death. Results: One hundred and two patients were stratified according to CLIPi score, being the majority classified as low risk. Patients with intermediate or high risk presented disease progression more frequently than those with low risk (PR: 1.2 / p = 0.004 / 95%CI: 1.0 - 1.6). The same did not occur with the variable related death. In addition, survival rates were not consistent with risk stratification. Study Limitations: Small sample and its retrospective analysis. Conclusions: Since CLIPi score was proposed, four other studies that we could consult showed conflicting results, similar to the present study. Further studies are necessary for a recommendation of its use.

Facial Papules in Frontal Fibrosing Alopecia: Beyond Vellus Hair Follicle Involvement.

BACKGROUND: Frontal fibrosing alopecia (FFA) is considered a variant of lichen planopilaris affecting mainly the frontotemporal hairline. Since the first report in 1994, several other clinical features have been associated with the disease, such as facial papules (FP). Even though FP have been linked to facial vellus hair follicle involvement, how this finding alone could lead to the formation of clinically evident FP in FFA patients had not yet been addressed. OBJECTIVE: To describe histopathological findings of FP in the context of FFA and to highlight features that may be linked to their clinical formation. METHODS: Cutaneous FP biopsies of FFA patients performed between January 2016 and May 2017 were retrieved from our pathology database and reexamined by 2 pathologists. RESULTS: Histological sections of thirteen 3.0-mm punch biopsy specimens (2 horizontally and 11 vertically oriented) were collected from 7 patients. Eleven specimens demonstrated prominent sebaceous glands and 10 dilated sebaceous ducts. Pinkus acid orcein staining revealed reduction and fragmentation of the elastic fibers in 12 samples and, in 7 of these, this finding was observed in both the papillary and reticular dermis, particularly around sebaceous lobules. Vellus hair follicle involvement was only seen in 2 samples. CONCLUSIONS: Prominent sebaceous lobules with dilated ducts associated with an abnormal elastic framework seem to be the main explanation for the formation of FP in the context of FFA.

Evaluation of the Cutaneous Lymphoma International Prognostic Index in patients with early stage mycosis fungoides.

BACKGROUND: Mycosis fungoides (MF) is the most common subtype of cutaneous T-cell lymphoma. TNMB system is the staging method used in MF, and it not only guides therapeutic management, but represents the main prognostic factor. In order to improve the prognostic evaluation, the Cutaneous Lymphoma International Prognostic Index (CLIPi) was proposed. OBJECTIVE: To evaluate the performance of CLIPi score for prognostic analysis in patients with early stage MF. METHODS: This is a retrospective cross-sectional observational study, with exploratory analysis. The outcome variables were disease progression and related death. RESULTS: One hundred and two patients were stratified according to CLIPi score, being the majority classified as low risk. Patients with intermediate or high risk presented disease progression more frequently than those with low risk (PR: 1.2 / p = 0.004 / 95%CI: 1.0 - 1.6). The same did not occur with the variable related death. In addition, survival rates were not consistent with risk stratification. STUDY LIMITATIONS: Small sample and its retrospective analysis. CONCLUSIONS: Since CLIPi score was proposed, four other studies that we could consult showed conflicting results, similar to the present study. Further studies are necessary for a recommendation of its use.

Idiopathic histiocytoid Sweet syndrome: a case report with clinical and histopathological considerations.

BACKGROUND: Histiocytoid Sweet syndrome is characterized by a predominant neutrophilic dermal infiltrate. Usual clinical differential diagnosis includes erythema multiforme, drug eruption, and erythema nodosum. Histiocytoid Sweet syndrome is considered an uncommon histopathological variant of the disease. METHODS: We evaluated clinical, histopathological, and immunohistochemical findings of a case categorized as idiopathic histiocytoid Sweet syndrome in which clinical-epidemiological data raised the possibilities of Sweet syndrome, leprosy, and drug reaction. RESULTS: Positive reaction to myeloperoxidase (MPO) in histiocytoid cells of the dermal infiltrate, response to oral corticosteroids, clinical and laboratory investigation, and absence of cutaneous lesions or clinical complaints within 1 year of follow-up are consistent with the diagnosis of idiopathic histiocytoid Sweet syndrome. CD68 (PG-M1) and CD15 positive cells were also present among dermal cells. CONCLUSIONS: Epidemiological data are relevant while considering a clinical differential diagnosis of Sweet syndrome that can be further expanded, from a histopathological point of view, when dealing with the histiocytoid variant since neutrophils, macrophages, and immature myelomonocytic cells with histiocytoid morphology are present. The significance of the MPO positive mononuclear dermal cells are not completely established.

Clinical and epidemiological profile of patients with early stage mycosis fungoides.

BACKGROUND: Mycosis fungoides is the most common form of primary cutaneous lymphoma, with an indolent, slowly progressive course and 88% five-year survival rate. The diagnosis is challenging, especially in the early stages, and usually relies on a good clinical-histopathological correlation. OBJECTIVE: The aim was to establish the clinical and epidemiological profile of patients with early-stage mycosis fungoides. METHODS: This was a retrospective cross-sectional observational study with an exploratory analysis. Outcome variables were disease progression and mycosis fungoides-related death. RESULTS: One hundred and two patients were included. The majority were white males, with a mean age of 55.6 years. Mean time from onset of lesions to diagnosis was 51.08 months. The majority of patients were classified as IB stage according to TNMB. Mean follow-up time was 7.85 years. Disease progression was seen in 29.4% of the patients. Death related to the disease occurred in 7.9% of patients. Plaque lesions, involvement of more than 10% of the body surface, altered lactate dehydrogenase and beta-2-microglobulin, and stage IB were significantly associated with disease progression, and altered lactate dehydrogenase and beta-2-microglobulin also correlated with higher frequency of deaths. STUDY LIMITATIONS: Small sample and retrospective design. CONCLUSIONS: The clinical and epidemiological profile of patients with early-stage mycosis fungoides in our sample corroborates reports in the literature. Diagnostic delay in our series is also consistent with previous findings, but the rate of disease progression, despite treatment, was higher than reported in the literature.