Tofacitinib as a possible treatment for skin thickening in diffuse cutaneous systemic sclerosis.

OBJECTIVES: To analyse the effectiveness of tofacitinib for the treatment of refractory skin thickening in dcSSc. METHODS: Data from 10 patients with dcSSc treated with tofacitinib (5 mg twice daily) were analysed. A total of 12 dcSSc patients treated with intensive conventional immunosuppressants were selected as the historical comparator group. A clinically relevant response was defined as a decrease in the modified Rodnan skin score (mRSS) of >5 points and ≥25% from baseline. Clinical indicators were compared between the two groups to evaluate the effect of tofacitinib. RESULTS: The mRSS significantly improved the first month after tofacitinib treatment, with a mean change in the mRSS of -3.7 (95% CI -5.52, -1.88; P = 0.001) and greater than the comparators at 6 months [-10.0 (95% CI -14.74, -5.26) vs -4.1 (95% CI -7.49, -0.73), P = 0.026]. Tofacitinib-treated patients had a significantly shorter response time than the comparators (P = 0.015 by log-rank test), with overall response rates of 20% (2/10) vs 0% (0/12) and 60% (6/10) vs 16.7% (2/12) at 1 and 3 months, respectively. CONCLUSION: Our results indicate that tofacitinib may be as effective as or even better than intensive conventional immunosuppressants, with a quicker and higher response rate in refractory dcSSc patients with progressive skin thickness.

Full axillary lymph node dissection and increased breast epidermal thickness 1 year after radiation therapy for breast cancer.

BACKGROUND: We previously reported a prospective study showing axillary lymph node dissection (ALND) is associated with increased breast skin thickening during and 6 weeks post-radiation therapy (RT), and now report ALND's long-term impact at 1 year. METHODS: Among 66 women who received whole breast RT after lumpectomy, objective ultrasound measurements of epidermal thickness over four quadrants of the treated breast were measured at five time points: before RT, week 6 of RT, and 6 weeks, 6 months, and 1 year post-RT. Skin thickness ratio (STRA) was generated by normalizing for corresponding measurements of the contralateral breast. RESULTS: A total of 2,436 ultrasound images were obtained. Among 63 women with evaluable data at 1 year, mean STRA significantly increased at 6 months (absolute mean increase of 65%, SD 0.054), and remained elevated at 1 year post-RT (absolute mean increase of 44%, SD 0.048). In multivariable analysis, ALND compared to sentinel lymph node biopsy, longer interval between surgery and RT, increased baseline STRA, and Caucasian race predicted for more severe changes in STRA at 1 year compared to baseline (all P < .05). CONCLUSIONS: In the setting of whole breast RT, our findings suggest that ALND has long-term repercussions on breast skin thickening.

Treatment of scleredema adultorum of Buschke with intravenous immunoglobulin and mycophenolate mofetil in a 14-year-old girl: a case report.

BACKGROUND: Scleredema adultorum of Buschke is a rare disease characterized by firm and non-pitting edema of the skin. The condition is rare with unknown etiology. Diagnosis is made on the basis of clinical findings and skin biopsy. CASE PRESENTATION: Here, we describe a 14-year-old Iranian girl presenting with non-pitting edema and woody thickening of the skin that progressed within a month. She was evaluated for possible underlying malignancy or connective tissue disorders, which were excluded by multiple laboratory workups. She underwent a skin biopsy which confirmed the diagnosis of scleredema, and she was successfully treated with intravenous immunoglobulin and mycophenolate mofetil. CONCLUSION: While scleredema adultorum of Buschke is a rare disease with no definite treatment, our effort through this report was to highlight the possible benefits of treatment by intravenous immunoglobulin and mycophenolate mofetil.

Second-trimester prenasal and prefrontal skin thickening - association with MECP2 triplication syndrome.

MECP2 triplication syndrome is a rare and usually lethal genetic disorder characterized by progressive neurologic and cognitive regression. None of the four reported cases describe prenatal sonographic features of affected offspring. We report a second-trimester fetus with marked prefrontal and prenasal skin thickening, retrognathia, and later, third-trimester mild cerebral ventriculomegaly. Amniocyte karyotype was normal male, but newborn whole-genome oligonucleotide microarray showed duplication and triplication of chromosome Xq28 containing the MECP2 gene. Comparative genomic hybridization may be diagnostic in fetuses with prefrontal and prenasal skin thickening, additional sonographic findings, and normal karyotype.

IgG4-related mastitis characterized by skin thickening of the breast: a case report.

BACKGROUND: IgG4-related diseases are characterized by marked infiltration and IgG4-positive plasma cells and fibrosis, and involve multiple organs. However, IgG4-related mastitis is rare. We report a case of mastitis associated with IgG4-related disease. CASE PRESENTATION: A 78-year-old woman visited our hospital with a complaint of multiple subcutaneous nodules. A biopsy of a dorsal subcutaneous mass was performed but did not yield a definitive diagnosis. However, blood tests showed a high level of IgG4, thus she was referred to the department of collagen disease for further examination. Computed tomography (CT) showed a thickening of the skin of the right breast, and the patient was referred to our department. On physical examination, a large area of thickened skin was observed in the right breast without inflammatory breast cancer-like redness, and no mass was palpable. A needle biopsy was performed on an indistinct hypoechoic area in the breast, and she was diagnosed with mastitis associated with IgG4-related disease. Systemic steroid therapy was then administered and the symptoms of multiple skin nodules and mastitis improved. CONCLUSIONS: We reached the diagnosis based on a biopsy of the mammary gland enabling the patient to begin treatment for IgG4-related disease. This case was characterized by breast skin thickening, which is different from inflammatory breast cancer.

MRI Changes in Breast Skin Following Preoperative Therapy for Patients with Inflammatory Breast Cancer.

RATIONALE AND OBJECTIVES: Preoperative systemic therapy (PST) followed by mastectomy and radiation improves survival for patients with inflammatory breast cancer (IBC). Residual disease within the skin post-PST adversely impacts surgical outcome and risk of local-regional recurrence (LRR). We aimed to assess magnetic resonance imaging (MRI) breast skin changes post-PST with pathologic response and its impact on surgical resectability. MATERIALS AND METHODS: We retrospectively reviewed 152 baseline and post-PST breast MRIs of 76 patients with IBC. Using the ACR-BIRADS MRI lexicon, we correlated skin thickness, qualitative enhancement, and kinetic analysis with pathologic response in the skin at mastectomy. RESULTS: Baseline MRI showed skin thickening in all 76 patients, 75/76 (99%) showed skin enhancement, 54/75 (72%) had medium/fast initial kinetics, usually with persistent delayed kinetics in 49/54 (91%). Following PST, 66/76 (87%) had residual skin thickening with 64/76 (84%) showing a decrease; 33/76 (43%) had persistent enhancement. The median thickness post-PST was 4.7 mm with residual tumor in the skin, and 3.0 mm without residual tumor (p = 0.008). Regardless of pathologic response, the majority of patients had persistent skin thickening on MRI following PST (100% [14/14] with residual tumor and 84% [52/62] without residual tumor). There was no association between post-PST skin thickness on breast MRI and rate of LRR. CONCLUSION: Patients with IBC have skin thickening and enhancement on baseline breast MRI, with a statistically significant reduction in skin thickness following successful PST. Despite persistent skin changes on MRI, patients achieving a partial or complete parenchymal response to PST may proceed to mastectomy with low LRR rates.

Scleredema with biopsy-confirmed cardiomyopathy: A case report.

Scleredema is a rare cutaneous mucinosis characterized by diffuse swelling and non-pitting induration. A 63-year-old man reported a 5-year history of skin thickening of the trunk and a 3-week history of dyspnea. Echocardiography revealed diffuse hypokinesis. Skin biopsies obtained from the waist showed thickened dermis with mucin. Myocardial biopsies showed alcian blue-stained tissue between the muscle fibers. The patient was referred to a dermatologist for phototherapy. Cardiomyopathy should be considered in patients with scleredema. Scleredema usually has a good prognosis; however, the mortality risk could be high when accompanied by cardiomyopathy.

Photoacoustic and high-frequency ultrasound imaging of systemic sclerosis patients.

INTRODUCTION: Systemic sclerosis starts with an early phase characterized by Raynaud's phenomenon, puffy fingers/hands, autoantibodies, and a scleroderma nailfold microscopic pattern. Alterations in the nailfold microscopic pattern are not evident in all early SSc patients. Photoacoustics (PA) and high-frequency ultrasound (HFUS) could fulfill this need. The former can measure oxygen saturation while the latter can measure skin thickening. We hypothesize that photoacoustics and high-frequency ultrasound can distinguish (early) SSc patients from individuals with primary Raynaud's phenomenon (PRP) by measuring oxygenation of the fingertip and skin thickening. METHODS: We compared measurements of oxygenation and skin thickness of the third finger between (early) SSc patients and PRP individuals and healthy controls. The spearman rank correlation was used to analyze an association between capillary density and oxygen saturation of the fingers. RESULTS: Thirty-one adult subjects participated in this study: twelve patients with SSc, 5 patients with early SSc, 5 volunteers with PR, and 9 healthy controls. We found a significant difference in oxygen saturation between (early) SSc patients (80.8% ± 8.1 and 77.9% ± 10.5) and individuals with PRP (93.9% ± 1.1). Measurements of skin thickening showed a significant difference in (early) SSc patients compared to individuals with PRP (0.48 ± 0.06 mm and 0.51 ± 0.16 mm vs. 0.27 ± 0.01 mm). There was no significant difference between healthy and PRP individuals in oxygenation or skin thickening. CONCLUSION: Photoacoustic and high-frequency ultrasound could help to distinguish between (early) SSc, PRP, and healthy individuals in both oxygenation and skin thickening.

Inflammatory breast cancer appearance at presentation is associated with overall survival.

BACKGROUND: Inflammatory breast cancer (IBC) is a clinical diagnosis. Here, we examined the association of a "classic" triad of clinical signs, swollen involved breast, nipple change, and diffuse skin change, with overall survival (OS). METHOD: Breast medical photographs from patients enrolled on a prospective IBC registry were scored by two independent reviewers as classic (triad above), not classic, and difficult to assign. Chi-squared test, Fisher's exact test, and Wilcoxon rank-sum test were used to assess differences between patient groups. Kaplan-Meier estimates and the log-rank test and Cox proportional hazard regression were used to assess the OS. RESULTS: We analyzed 245 IBC patients with median age 54 (range 26-81), M0 versus M1 status (157 and 88 patients, respectively). The classic triad was significantly associated with smoking, post-menopausal status, and metastatic disease at presentation (p = 0.002, 0.013, and 0.035, respectively). Ten-year actuarial OS for not classic and difficult to assign were not significantly different and were grouped for further analyses. Ten-year OS was 29.7% among patients with the classic sign triad versus 57.2% for non-classic (p < 0.0001). The multivariate Cox regression model adjusting for clinical staging (p < 0.0001) and TNBC status (<0.0001) demonstrated classic presentation score significantly associated with poorer OS time (HR 2.6, 95% CI 1.7-3.9, p < 0.0001). CONCLUSIONS: A triad of classic IBC signs independently predicted OS in patients diagnosed with IBC. Further work is warranted to understand the biology related to clinical signs and further extend the understanding of physical examination findings in IBC.

Why diagnosing inflammatory breast cancer is hard and how to overcome the challenges: a narrative review.

OBJECTIVE: The purpose of this narrative review is to summarize the contributors to misdiagnosis or delayed diagnosis of inflammatory breast cancer (IBC) and strategies for expedient diagnosis. BACKGROUND: Patients with IBC often report the disease as initially being misdiagnosed, most commonly as mastitis. METHODS: We reviewed the literature on this challenging diagnosis by using sequential PubMed search criteria including IBC breast symptoms, IBC diagnosis, and IBC imaging modalities to augment the authors' knowledge of IBC. Other references were added from the manuscripts identified in the PubMed searches and from manuscript reviewers. CONCLUSIONS: Several factors contribute to the delayed diagnosis of IBC. One important factor is that IBC is uncommon, and many generalists may not be aware of it in the differential diagnosis of breast skin symptoms. Several features of IBC contribute to the low sensitivity of mammography for its detection, and so the diagnosis is based on clinical factors and is thereby subjective. The presentation can be highly varied; classic textbook images that do not capture the range of presenting signs and symptoms across skin tones may contribute to missed diagnoses in patients with atypical presentations. In fact, the staging system of the American Joint Committee on Cancer, which requires erythema of the breast skin for diagnosis, may exclude patients with obvious global breast skin findings that are not explicitly red. We present an adapted algorithm for working up the undiagnosed inflammatory breast to ensure the timely and accurate diagnosis of IBC. We assert that frank, non-erythematous global skin signs in an enlarged breast with diffuse breast malignancy are sufficient to diagnose IBC if the timing of these signs and findings on biopsy are consistent. We further provide images of atypical IBC identified by global breast skin signs, including peau d'orange, consistent with IBC in the absence of frank erythema.

Early trajectories of skin thickening are associated with severity and mortality in systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) is a severe and highly heterogeneous disease. The modified Rodnan skin score (mRSS) is a widely used tool for the assessment of the extent and degree of skin thickness. This study aimed to identify the classes of patients with early similar skin thickening trajectories without any a priori assumptions and study their associations with organ involvement and survival. METHODS: From the French SSc national cohort, patients with a disease duration of less than 2 years at inclusion and with at least 2 mRSS available within the first 4 years of follow-up were enrolled. Classes of patients with similar mRSS trajectories were identified based on a latent class mixed model. The clinical characteristics and survival rate were compared between the obtained classes. RESULTS: A total of 198 patients fulfilled the inclusion criteria, with a total of 641 mRSS available. The median disease duration and follow-up were 0.8 (interquartile range 0.4; 1.2) and 6.3 (3.8; 8.9) years, respectively. Individual trajectories of mRSS were highly heterogeneous between patients. Models with 1-6 latent classes of trajectories were sequentially assessed, and the 5-class model represented the best fit to data. Each class was characterized by a unique global trajectory of mRSS. The median disease duration did not differ significantly between classes. Baseline organ involvement was more frequent in classes with significant change over time (classes 2-5) than in class 1 (low baseline mRSS without significant change over time). Using Cox regression, we observed a progressively increasing risk of death from classes 1 to 5. CONCLUSIONS: Early identification of clinical phenotype based on skin thickening trajectories could predict morbi-mortality in SSc. This study suggested that mRSS trajectories characterization might be pivotal for clinical practice and future trial designs.

Feet Deformity and Gait Disturbance in a Patient with Pachydermoperiostosis (PDP). Case Study.

Pachydermoperiostosis is a rare condition representing a primary form of hypertrophic osteoarthropathy. It presents in different stages. Patients often overlook early symptoms, because they are benign. The most common manifestations are clubbing of the fingers and toes, skin thickening with characteristic folds on the face and head and widening of joints accompanied by radiological changes. Surgical treatment is not often needed, and, consequently, there are no strict guidelines on surgical management, which is mainly based on case report ana-lysis. This paper presents a case of surgical management of pachydermoperiostosis.

Diagnostic Accuracy of Digital Mammography in the Detection of Breast Cancer.

Introduction Breast cancer has a high prevalence in the community and places very high demands on resources. Digital mammography provides a good quality image with reduced radiation dose and can detect breast carcinoma in its earlier stages, resulting in good prognosis and improved patient survival. Objective To calculate the diagnostic accuracy of digital mammography in the detection of breast cancer, using histopathology as a gold standard in women aged over 30 years, who are undergoing mammography for screening and diagnostic purposes. Materials and methods This was a cross-sectional analytical study, conducted in the department of radiology, for a total duration of 10 months. A total of 122 patients of age above 30 years, referred for digital mammography for the evaluation of different symptoms related to breast diseases, followed by biopsy/surgery and histopathology, were included in the study. Result Our data confirmed that digital mammography is a highly accurate tool for breast cancer detection having a sensitivity of 97%, a specificity of 64.5%, a positive predictive value of 89%, and a negative predictive value of 90.9%, with a diagnostic accuracy of 89.3%. Conclusion Considering our results, we recommend that digital mammography should replace screen-film mammography as a basic tool to detect breast cancer for both screening and diagnostic purposes.

Bovine besnoitiosis (Besnoitia besnoiti) in an Irish dairy herd.

Bovine besnoitiosis, caused by the apicomplexan protozoan parasite Besnoitia besnoiti, was diagnosed in an Irish dairy herd. This is the first diagnosis of besnoitiosis in Ireland or the UK and the most northerly European outbreak yet described. The diagnosis occurred following a farm investigation in June 2015 into an unusual dermatological problem that had been ongoing since 2010. On an annual basis, 1-2 per cent of cows in the herd exhibited clinical signs, including skin thickening, alopecia, weight loss and poor performance. Others displayed pyrexia, limb oedema, respiratory distress and reduced milk yield. Histopathological examination of skin revealed granulomatous and eosinophilic dermatitis, with characteristic intradermal protozoal cysts, consistent with cutaneous besnoitiosis. Follow-up serological testing and clinical examination of cattle (n=228) on the farm found that 68 per cent (144/212) were seropositive for B. besnoiti In addition, 51 per cent (117/228) had characteristic scleral conjunctival cysts and 68 per cent (134/198) had vulval cysts. Postmortem examination of a severely affected animal revealed typical gross and histopathological lesions of B. besnoiti infection. These results confirmed endemic infection with B. besnoiti The identification of this exotic disease highlights the importance of veterinary surveillance at both local and national level, particularly in relation to emerging diseases.

Review of ultrasound appearance in inflammatory breast cancer: A pictorial essay.

Inflammatory breast cancer (IBC) is a rare malignancy accounting for 1-2% of breast cancers. It has an aggressive clinical presentation and poor prognosis. The sonographic findings in 41 patients with a clinical diagnosis of IBC and biopsy-proven breast malignancy are presented in this study. The most common finding was the presence of skin thickening (92%). Multiple small anechoic spaces within the dermis, correlating with the presence of dermal lymphatic invasion by tumour emboli on histopathology were noted in approximately one-third of cases. Other sonographic findings included single or multiple masses, parenchymal oedema, axillary lymphadenopathy, echogenic foci consistent with microcalcifications and increased vascularity.

Risk factors for severity and manifestations in systemic sclerosis and prediction of disease course.

Systemic sclerosis (SSc, or scleroderma) is a rheumatic disease with distinct features that encompass autoimmunity, vascular lesions (vasculopathy) and tissue fibrosis. The disease has a high morbidity and mortality compared with other rheumatic diseases. This review discusses risk factors and markers that predict the disease course and the occurrence of disease manifestations, with an emphasis on major organ involvement. In addition, risk factors will be described that are associated with mortality in SSc patients. The review addresses the impact of recent developments on screening, diagnosis and risk stratification as well as the need for further research where data are lacking.

Nutritional status measured by BMI is impaired and correlates with left ventricular mass in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a multisystemic chronic disease that is complicated by protein-energy malnutrition (PEM). Considering that PEM also may influence left ventricular mass (LVM), the aim of this study was to evaluate whether LVM is related to patients' nutritional status and to determine clinically relevant features of SSc. METHODS: Adult patients referring to our institution were considered. Body weight, height, body mass index (BMI), involuntary weight loss, and the presence of gastrointestinal symptoms were recorded. Echocardiography was performed to assess LVM, using the Devereux regression formula. Results were then normalized by body surface area. Pattern, skin thickening, disease activity and severity, and duration were assessed to characterize SSc. RESULTS: Ninety-four patents with SSc (81 women and 13 men; median duration of disease 7 y) were studied. The prevalence of PEM as assessed by BMI < 20 kg/m(2) was 19%, whereas 15% of patients reported involuntary weight loss of any degree. Patients who lost weight reported gastrointestinal symptoms more frequently (P < 0.05). PEM was not associated with disease activity. LVM (g/m(2)) correlated with patients' BMI (r = 0.32; P < 0.01), and the vascular domain of disease severity (DDS; r = 0.21; P < 0.05), but it showed a negative correlation with skin thickening (r = -0.21 P = 0.01). Patients with ulcers had a significantly greater LVM than patients without skin lesions. CONCLUSIONS: Our study shows that LVM correlates with patients' BMI, skin thickening, and the vascular domain of DSS. Therefore, LVM could serve as a marker of nutritional status and fibrosis in patients with SSc.