Limited effect of reducing pulmonary tuberculosis incidence amid mandatory facial masking for COVID-19.

Although the incidence and mortality rates associated with tuberculosis (TB) have been decreasing in many countries, TB remains a major public health concern. Obligatory facial masking and reduced health-care capacity because of COVID-19 may substantially influence TB transmission and care. The Global Tuberculosis Report 2021 published by the World Health Organization indicated a TB rebound at the end of 2020, which coincided with the COVID-19 pandemic. We explored this rebound phenomenon in Taiwan by investigating whether TB incidence and mortality are affected by COVID-19 because of their common route of transmission. In addition, we investigated whether the incidence of TB varies across regions with different incidences of COVID-19. Data (2010-2021) regarding annual new cases of TB and multidrug-resistant TB were collected from the Taiwan Centers for Disease Control. TB incidence and mortality were assessed in Taiwan's seven administrative regions. Over the last decade, TB incidence decreased continually, even during 2020 and 2021, the years coinciding with the COVID-19 pandemic. Notably, TB incidence remained high in regions with low COVID-19 incidence. However, the overall decreasing trends of TB incidence and mortality remained unchanged during the pandemic. Facial masking and social distancing may prevent COVID-19 transmission but exhibit limited efficacy in reducing TB transmission. Thus, during health-related policymaking, policymakers must consider TB rebound, even in the post-COVID-19 era.

Selective AhR knockout in langerin-expressing cells abates Langerhans cells and polarizes Th2/Tr1 in epicutaneous protein sensitization.

The aryl hydrocarbon receptor (AhR) represents an environmental sensor regulating immune responses. In the skin, AhR is expressed in several cell types, including keratinocytes, epidermal Langerhans cells (LC), and dermal dendritic cells (DC). The mechanisms how AhR activates or inhibits cutaneous immune responses remain controversial, owing to differences in the cell-specific functions of AhR and the different activating ligands. Therefore, we sought to investigate the role of AhR in LC and langerin+ and negative DC in the skin. To this aim, we generated Langerin-specific and CD11c-specific knockout (-/-) mice lacking AhR, respectively, in LC and Langerin+ dermal DC and in all CD11c+ cells. These were then tested in an epicutaneous protein (ovalbumin, Ova) sensitization model. Immunofluorescence microscopy and flow cytometry revealed that Langerin-AhR-/- but not CD11c-AhR-/- mice harbored a decreased number of LC with fewer and stunted dendrites in the epidermis as well as a decreased number of LC in skin-draining lymph nodes (LN). Moreover, in the absence of AhR, we detected an enhanced T helper type-2 (Th2) [increased interleukin 5 (IL-5) and interleukin 13 (IL-13)] and T regulatory type-1 (Tr1) (IL-10) response when LN cells were challenged with Ova in vitro, though the number of regulatory T cells (Treg) in the LN remained comparable. Langerin-AhR-/- mice also exhibited increased blood levels of Ova-specific immunoglobulin E (IgE). In conclusion, deletion of AhR in langerin-expressing cells diminishes the number and activation of LC, while enhancing Th2 and Tr1 responses upon epicutaneous protein sensitization.

Taiwanese dermatological association consensus for the definition, classification, diagnosis, and management of urticaria: A 2021 update.

Urticaria is a prevalent disease with substantial physical, psychological, and economic impacts. With the advent of understandings of the disease and the emerging evidence of treatments, the international guidelines for treating urticaria have been updated in recent years. In order to update the 2014 edition of the Taiwanese Dermatological Association (TDA) consensus of urticaria, a total of 17 dermatologists with extensive experience in urticaria management were invited to and attended the TDA consensus meetings. All the specific aspects of the content were approved by at least 75% of the experts in attendance. Comparing to the former edition, several substantial modifications were made. For diagnosis, D-dimer was added as the recommended routine test in patients with chronic spontaneous urticaria. For pharmacological management, treatment suggestions were simplified. The approved-dosed, the up-dosed second-generation antihistamines, omalizumab, and cyclosporine were listed as the first-line to the fourth-line treatment, respectively. In addition, the management for patients of special considerations, such as the elderly, children, and pregnant women, were all discussed and mentioned in the consensus. We hope the updated TDA consensus can serve as a reference for all physicians and can help the physicians providing up-to-dated managements for these patients.

Lifetime Increased Risk of Adult Onset Atopic Dermatitis in Adolescent and Adult Patients with Food Allergy.

Food allergy can result in life-threatening anaphylaxis. Atopic dermatitis (AD) causes intense itching and impaired quality of life. Previous studies have shown that patients with classical early-onset AD tend to develop food allergy and that 10% of adults with food allergies have concomitant AD. However, it is not known whether late-onset food allergy leads to adult-onset AD, a recently recognized disease entity. Using an initial cohort of one-million subjects, this study retrospectively followed-up 2851 patients with food allergy (age > 12 years) for 14 years and compared them with 11,404 matched controls. While 2.8% (81) of the 2851 food allergy patients developed AD, only 2.0% (227) of the 11,404 controls developed AD. Multivariate regression analysis showed that food allergy patients were more likely to develop AD (adjusted hazard ratio = 2.49, p < 0.0001). Controls had a 1.99% risk of developing AD, while food allergy patients had a significantly higher risk (7.18% and 3.46% for patients with ≥3 and <3 food allergy claims, respectively) of developing adult-onset AD. This is the first study to describe the chronological and dose-dependent associations between food allergy in adolescence and the development of adult-onset AD.

Dermal dendritic cells, but not Langerhans cells, are critical in murine single epicutaneous sensitization.

A murine repeated protein-patch model has been established to study epicutaneous sensitization in atopic dermatitis. This model has shown a predominant Th2 and a weak Th1 response in both BALB/c and C57BL/6 mice. However, Th responses induced in the repeated model are not consistent with the generally accepted theory that BALB/c and C57BL/6 mice are Th2 and Th1 prone and are representatives of human atopy and non-atopy, respectively. In this study, a single protein-patch model was established, which showed in addition to the Th2 response, a remarkable Th1 response in C57BL/6 mice, but not in BALB/c mice. Moreover, using muLangerin-DTR mice, we demonstrated that dermal dendritic cells, but not Langerhans cells, are critical in single epicutaneous sensitization in both strains of mice.

Molecular Mechanisms of UV-Induced Apoptosis and Its Effects on Skin Residential Cells: The Implication in UV-Based Phototherapy.

The human skin is an integral system that acts as a physical and immunological barrier to outside pathogens, toxicants, and harmful irradiations. Environmental ultraviolet rays (UV) from the sun might potentially play a more active role in regulating several important biological responses in the context of global warming. UV rays first encounter the uppermost epidermal keratinocytes causing apoptosis. The molecular mechanisms of UV-induced apoptosis of keratinocytes include direct DNA damage (intrinsic), clustering of death receptors on the cell surface (extrinsic), and generation of ROS. When apoptotic keratinocytes are processed by adjacent immature Langerhans cells (LCs), the inappropriately activated Langerhans cells could result in immunosuppression. Furthermore, UV can deplete LCs in the epidermis and impair their migratory capacity, leading to their accumulation in the dermis. Intriguingly, receptor activator of NF-κB (RANK) activation of LCs by UV can induce the pro-survival and anti-apoptotic signals due to the upregulation of Bcl-xL, leading to the generation of regulatory T cells. Meanwhile, a physiological dosage of UV can also enhance melanocyte survival and melanogenesis. Analogous to its effect in keratinocytes, a therapeutic dosage of UV can induce cell cycle arrest, activate antioxidant and DNA repair enzymes, and induce apoptosis through translocation of the Bcl-2 family proteins in melanocytes to ensure genomic integrity and survival of melanocytes. Furthermore, UV can elicit the synthesis of vitamin D, an important molecule in calcium homeostasis of various types of skin cells contributing to DNA repair and immunomodulation. Taken together, the above-mentioned effects of UV on apoptosis and its related biological effects such as proliferation inhibition, melanin synthesis, and immunomodulations on skin residential cells have provided an integrated biochemical and molecular biological basis for phototherapy that has been widely used in the treatment of many dermatological diseases.

The pathophysiology and current treatments for the subcutaneous panniculitis-like T cell lymphoma: An updated review.

Subcutaneous panniculitis-like T cell lymphoma (SPTCL) is a rare cutaneous T cell lymphoma, which is indolent in nature but could claim life if not correctly diagnosed and promptly treated. SPTCL is usually presented clinically as painless subcutaneous and erythematous nodules over the trunk or extremities. Active clinical vigilance for these subcutaneous nodules or panniculitis-like lesions is warranted. A biopsy must be performed in order to make a correct diagnosis. Positron emission tomography scan is utilized for disease staging and treatment follow-up. Due to the rarity of this lymphoma, a standard treatment protocol is not established yet. However, most cases of SPTCL could be treated well under immunosuppressive or polychemotherapeutic drugs except in cases with hemophagocytic syndrome. Hematopoietic stem cell transplantation may be used in refractory or relapse cases. In this review, we presented a case of SPTCL with long-term complete remission. Meanwhile, since most clinical evidences and experiences of SPTCL are based mostly on case reports or small case series, and the understanding of the SPTCL pathophysiology is limited, we reviewed and updated the pathophysiology and treatments of SPTCL.

Gasdermin A Is Required for Epidermal Cornification during Skin Barrier Regeneration and in an Atopic Dermatitis-Like Model.

Atopic dermatitis is featured with impaired skin barrier. The stratum corneum and the intercellular tight junctions constitute the permeability barrier, which is essential to protect water loss in the host and prevent pathogen entry. The epidermal barrier is constantly renewed by differentiating keratinocytes through cornification, during which autophagy contributes to elimination of organelles and nucleus. The human GSDMA and its mouse homologs Gsdma1-3 are expressed in the suprabasal epidermis. Although a pyroptotic role of GSDMA/Gsdma1 in host defense against Streptococcus pyogenes has been reported, the physiological function of Gsdma1/a2/a3 in epidermal homeostasis remains elusive. Here, through repeated epidermal barrier disruption, we found that tight junction formation and stratum corneum maturation were defective in the Gsdma1/a3-deficient epidermis. Using comparative gene profiling analysis, mitochondrial respiration measurement, and in vivo tracing of mitophagy, our data indicate that Gsdma1/a3 activation leads to mitochondrial dysfunction and subsequently facilitates mitochondrial turnover and epidermal cornification. In calcipotriol (MC903)-induced atopic dermatitis-like animal model, we showed that Gsdma1/a3-deficiency selectively enhanced the T helper type 2 response. Remarkably, the GSDMA expression is reduced in the epidermis of patients with atopic dermatitis compared with that of normal individuals. Gsdma1/a3-deficiency might be involved in atopic dermatitis pathogenesis, likely through GSDMA-mediated epidermal differentiation and cornification.

Aberrant cell proliferation by enhanced mitochondrial biogenesis via mtTFA in arsenical skin cancers.

Arsenic-induced Bowen's disease (As-BD), a cutaneous carcinoma in situ, is thought to arise from gene mutation and uncontrolled proliferation. However, how mitochondria regulate the arsenic-induced cell proliferation remains unclear. The aim of this study was to clarify whether arsenic interfered with mitochondrial biogenesis and function, leading to aberrant cell proliferation in As-BD. Skin biopsy samples from patients with As-BD and controls were stained for cytochrome c oxidase (Complex IV), measured for mitochondrial DNA (mtDNA) copy number and the expression levels of mitochondrial biogenesis-related genes, including peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), nuclear respiratory factor 1 (NRF-1), and mitochondrial transcription factor A (mtTFA). The results showed that expression of cytochrome c oxidase, mtTFA, NRF-1, and PGC-1α was increased in As-BD compared with in healthy subjects. Treatment of primary keratinocytes with arsenic at concentrations lower than 1.0 µmol/L induced cell proliferation, along with enhanced mitochondrial biogenesis. Furthermore, we observed that the mitochondrial oxygen consumption rate and intracellular ATP level were increased in arsenic-treated keratinocytes. Blocking of mitochondrial function by oligomycin A (Complex V inhibitor) or knockdown of mtTFA by RNA interference abrogated arsenic-induced cell proliferation without affecting cyclin D1 expression. We concluded that mtTFA up-regulation, augmented mitochondrial biogenesis, and enhanced mitochondrial functions may contribute to arsenic-induced cell proliferation. Targeting mitochondrial biogenesis may help treat arsenical cancers at the stage of cell proliferation.

Recognition of tuberous sclerosis in adult women: delayed presentation with life-threatening consequences.

BACKGROUND: Tuberous sclerosis complex (TSC) is associated with tumor development in the brain, retina, kidney, skin, heart, and lung. Seizures, intellectual disability, and characteristic skin lesions commonly manifest in early childhood, but some findings, notably renal angiomyolipomas and pulmonary lymphangioleiomyomatosis (LAM), emerge later, placing adults with undiagnosed TSC at increased risk for morbidity and mortality. OBJECTIVE: To describe the clinical presentation and severity of TSC in adult women. DESIGN: Retrospective cohort study. SETTING: National Institutes of Health Clinical Center, Bethesda, Maryland, 1995 to 2010. PATIENTS: 79 women aged 18 years or older who were enrolled in an observational cohort study of TSC to evaluate disease manifestations. MEASUREMENTS: History, physical examination, pulmonary function testing, chest radiography, abdominal computed tomography, high-resolution chest computed tomography, and brain magnetic resonance imaging were used to evaluate patients. RESULTS: Among the 45 patients who received a diagnosis of TSC in adulthood, 21 presented with symptoms due to LAM, 19 with renal angiomyolipomas, and 10 with seizures. Of the 45 patients, 30 met clinical criteria for TSC in childhood that remained undiagnosed for a median of 21.5 years and 15 were older than 18 years before meeting the clinical criteria for TSC. Patients diagnosed in adulthood and those diagnosed in childhood had similar occurrences of pneumothorax, shortness of breath, hemoptysis, nephrectomy, and death. LIMITATION: No men were included in the study, and selection was biased toward patients having pulmonary LAM. CONCLUSION: Women who received a TSC diagnosis in adulthood had minimal morbidity during childhood but were still at risk for life-threatening pulmonary and renal manifestations. PRIMARY FUNDING SOURCE: Intramural Research Program, National Institutes of Health, National Heart, Lung, and Blood Institute.

IL-33 Enhances ACE2 Expression on Epidermal Keratinocytes in Atopic Dermatitis: A Plausible Issue for SARS-CoV-2 Transmission in Inflamed Atopic Skin.

BACKGROUND: Interleukin-33 (IL-33) is an important cytokine in the pathophysiology of atopic dermatitis (AD) and in the progression of COVID-19. Angiotensin converting enzyme 2 (ACE2), the entry receptor for SARS-CoV-2, is expressed in epidermal keratinocytes. Whether IL-33 could regulate the expression of ACE2 mechanistically in keratinocytes warrants investigation. OBJECTIVE: We questioned whether the ACE2 expression is increased in AD skin. We also questioned whether ACE2 is expressed in keratinocytes; if so, would its expression be enhanced mechanistically by IL-33. METHODS: We measured and compared the expression of ACE2 in skin from patients with AD, patients with psoriasis, and healthy controls using immunohistochemistry. Flow cytometry, immunofluorescent exam, and quantitative RT-PCR were used for measuring the ACE2 expression in cultured keratinocytes treated with IL-33 and IL-17. Blocking antibodies were utilized to study the intracellular signaling pathways governing the ACE2 expression using cytokines. RESULTS: The results showed that the ACE2 expression is increased in AD compared with that in healthy skin and psoriasis. In primary epidermal keratinocytes, ACE2 is constitutively expressed. IL-33 induces a time-dependent increase in ACE2 expression in cultured keratinocytes through quantitative PCR, flow cytometry, and immunofluorescent examinations. Furthermore, pretreatment of an ERK inhibitor, but not a STAT3 inhibitor, eliminated the increases in ACE2 by IL-33 in keratinocytes, indicating that IL-33 enhances ACE2 expression through ERK on epidermal keratinocytes. CONCLUSION: This is the first study to reveal that IL-33 enhances ACE2 expression on keratinocytes via ERK. Although further mechanistic studies are required, the increased ACE2 expression in IL-33 might have a biological implication on the transmission of SARS-CoV-2 in patients with AD.

A population-based study to estimate survival and standardized mortality of tuberous sclerosis complex (TSC) in Taiwan.

BACKGROUND: Tuberous sclerosis complex (TSC) is an autosomal dominant disease with systemic manifestations, which can cause significant mortality and morbidity. Population-based epidemiological studies on TSC mortality and survival remain scarce, though several recent studies provide evidence that TSC survival rates are high and disease prognosis is fair for most patients. This study aims to estimate the life expectancy and mortality statistics in Taiwanese TSC patients, investigate prognosis and associations of TSC mortality based on demographic variables, and compare these results to past literature, especially for Asian patients. METHODS: Taiwanese National Health Insurance (NHI) insurees can obtain Catastrophic Illness Certificates (CIC) for certain eligible diseases to waive copayments after diagnosis by two independent physicians. CIC holders for TSC during 1997-2010 were identified from the NHI Research Database. Queries on enrollment (CIC acquisition) age, endpoint (end of query period or death) age, sex, and comorbidities were obtained. Patients were separated into cohorts (endpoint age, sex, and age of diagnosis), and analyzed accordingly. RESULTS: 471 patients (232 male, 239 female) were identified, of which 14 died. Compared to literature, patients showed similar demographics (age range, diagnosis age, sex distribution); similar manifestations and prevalence (epilepsy, intellectual disability, renal disease); lower disease prevalence (1 in 63,290); lower mortality (0.21% per year); and near-identical standardized mortality ratio (4.99). A cumulative mortality of 4.08% was found over 14 years, though mortality plateaued at 7 years post-enrollment, suggesting a good overall survival rate; comparable with previous studies in Asian patients. Enrollment age was a significant prognostic factor, with late-enrollment (age > 18) patients at higher risk for all-cause mortality (Hazard ratio = 6.54). Average remaining lifetime was significantly lower than the general population, and decreased with age. CONCLUSIONS: This study reports a population-based disease database, highlights the importance of diagnosis age in prognosis prediction, and suggests the role of renal manifestations in mortality. Furthermore, it corroborates recent TSC studies in the Asian population in terms of survival. Overall, physician vigilance, early diagnosis, and careful monitoring are beneficial for disease outcome and patient survival.

Halved Incidence of Scrub Typhus after Travel Restrictions to Confine a Surge of COVID-19 in Taiwan.

Scrub typhus is a rickettsial disease that is usually transmitted by mite exposure. Infected patients may present with a fever, fatigue, headache, and muscle pain. A blackish skin lesion, called eschar, is pathognomic. The mortality rate in untreated cases is high. The first case of scrub typhus in Taiwan was reported in 1908 during the Japanese colonization. In this article, using the National Infectious Disease Statistics System (NIDSS) from the Taiwan CDC, we analyzed the dynamic incidence of scrub typhus from 2016 to 2021, both seasonally and geographically. In addition, we asked whether the recent travel restrictions and social distancing policy in Taiwan (19 May to 27 July 2021), implemented due to the COVID-19 outbreak, would change the incidence of scrub typhus. The results showed that scrub typhus was most common in summer, with an incidence almost twofold greater than that in winter or spring. Most cases were identified in rural regions. Interestingly, there was a significant 52% reduction in the summer incidence in 2021, compared to the average summer incidence of the past 5 years. This reduction coincided with the countrywide lockdown measures and travel restrictions. The restricted measures for outdoor activities may have contributed to the reduced incidence of scrub typhus.

GLUT-1 Enhances Glycolysis, Oxidative Stress, and Fibroblast Proliferation in Keloid.

A keloid is a fibroproliferative skin tumor. Proliferating keloid fibroblasts (KFs) demand active metabolic utilization. The contributing roles of glycolysis and glucose metabolism in keloid fibroproliferation remain unclear. This study aims to determine the regulation of glycolysis and glucose metabolism by glucose transporter-1 (GLUT-1), an essential protein to initiate cellular glucose uptake, in keloids and in KFs. Tissues of keloids and healthy skin were explanted for KFs and normal fibroblasts (NFs), respectively. GLUT-1 expression was measured by immunofluorescence, RT-PCR, and immunoblotting. The oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were measured with or without WZB117, a GLUT-1 inhibitor. Reactive oxygen species (ROS) were assayed by MitoSOX immunostaining. The result showed that glycolysis (ECAR) was enhanced in KFs, whereas OCR was not. GLUT-1 expression was selectively increased in KFs. Consistently, GLUT-1 expression was increased in keloid tissue. Treatment with WZB117 abolished the enhanced ECAR, including glycolysis and glycolytic capacity, in KFs. ROS levels were increased in KFs compared to those in NFs. GLUT-1 inhibition suppressed not only the ROS levels but also the cell proliferation in KFs. In summary, the GLUT-1-dependent glycolysis and ROS production mediated fibroblast proliferation in keloids. GLUT1 might be a potential target for metabolic reprogramming to treat keloids.

Arsenic leads to autophagy of keratinocytes by increasing aquaporin 3 expression.

Exposure to arsenic, a ubiquitous metalloid on Earth, results in human cancers. Skin cancer is the most common arsenical cancers. Both autophagy and aquaporin pathway are known to promote carcinogenesis. However, the mechanisms by which arsenic regulates aquaporin and autophagy in arsenical skin cancers remain elusive. This study aims to address how arsenic regulates aquaporin-3, the predominant aquaporin in epidermal keratinocytes, and how this process would induce autophagy. Quantitative real-time PCR and immunofluorescence were used to measure the expression of aquaporin 3 in arsenical skin cancers and arsenic-treated keratinocytes. Beclin-1 expression and autophagy were measured. We examined if blocking aquaporin 3 could interfere arsenic-induced autophagy in keratinocytes. Expression of aquaporin 3 is increased in arsenical cancers and in arsenic-treated keratinocytes. Arsenic induced autophagy in primary human keratinocytes. Notably, the arsenic-induced autophagy was inhibited by pretreatment of keratinocytes with aquaporin inhibitors Auphen or AgNO3, or RNA interference against aquaporin 3. The data indicates that the aquaporin 3 is an important cell membrane channel to mediate arsenic uptake and contributes to the arsenic-induced autophagy.

Risk of cancer development in patients with keloids.

Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998-2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.

CT of sclerotic bone lesions: imaging features differentiating tuberous sclerosis complex with lymphangioleiomyomatosis from sporadic lymphangioleiomymatosis.

PURPOSE: To determine if sclerotic bone lesions evident at body computed tomography (CT) are of value as a diagnostic criterion of tuberous sclerosis complex (TSC) and in the differentiation of TSC with lymphangioleiomyomatosis (LAM) from sporadic LAM. MATERIALS AND METHODS: Informed consent was signed by all patients in this HIPAA-compliant study approved by the institutional review board. Retrospective analysis was performed of the body CT studies of 472 patients: 365 with sporadic LAM, 82 with TSC/LAM, and 25 with TSC. The images were reviewed by using a picture archiving and communication system workstation with bone settings (window width, 1500 HU; window level, 300 HU) and fit-to-screen option. CT image characteristics assessed included shape, size, and distribution of sclerotic bone lesions with subsequent calculation of differences in the frequency of these lesions. RESULTS: Most commonly the sclerotic bone lesions were round, measured 0.3 cm (range, 0.2-3.2), and were distributed throughout the spine. The frequencies differed among the three patient groups Four or more sclerotic bone lesions were detected in all 25 (100%) of those with TSC, with a sensitivity of .89 (72 of 82) and specificity of .97 (355 of 367) in the differentiation of sporadic LAM from TSC/LAM (P < .01). CONCLUSION: The number of sclerotic bone lesions at body CT is of potential value in the diagnosis of TSC and in the differentiation of patients with sporadic LAM from those with TSC/LAM. (c) RSNA, 2010.

Acral lesions in tuberous sclerosis complex: insights into pathogenesis.

BACKGROUND: Patients with tuberous sclerosis complex (TSC) are predisposed to developing ungual fibromas and other acral lesions. OBJECTIVE: We sought to determine the numbers, types, and locations of acral skin lesions in TSC. METHODS: We examined and photographed 76 adult women with TSC. RESULTS: The age of the patients ranged from 20 to 69 years, with a mean age of 39 +/- 11 years. Ungual fibromas were observed in 61 of 76 patients (80%). Periungual fibromas were more common than subungual fibromas, were more common on the feet than the hands, and showed the greatest frequency on the fifth toe. Longitudinal grooves in the nails occurred with or without a visible fibroma. Longitudinal short red streaks--lesions that we term "red comets"--were observed in 22 patients (29%). Longitudinal leukonychia was observed in 14 patients (18%). One patient had isolated digital overgrowth and one patient had pachydermodactyly. LIMITATIONS: No men or children were included in this study. CONCLUSIONS: Examination of patients for skin lesions of TSC could be improved by including inspection for longitudinal nail grooves, red comets, longitudinal leukonychia, and splinter hemorrhages in addition to ungual fibromas. The anatomic distribution of TSC ungual fibromas is not random and appears consistent with trauma-promoted tumor formation.