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The Journal of Allergy and Clinical... Feb 2021Primary immune deficiencies (PIDs) are a heterogeneous group of disorders resulting from defects in immune system. They lead to increased susceptibility to infections...
BACKGROUND
Primary immune deficiencies (PIDs) are a heterogeneous group of disorders resulting from defects in immune system. They lead to increased susceptibility to infections and immune dysregulation. The resulting chronic inflammation can induce long-term complications, including AA amyloidosis (AAA).
OBJECTIVES
To present the French cases of PID-related AAA and perform a systematic literature review to determine its main features and predisposing factors.
METHODS
A systematic literature review was performed by searching MEDLINE up until 2019. New French cases were identified with the help of the Reference Center for Auto-Inflammatory Diseases and AA Amyloidosis and the Reference Center for Hereditary Immune Deficiencies.
RESULTS
Forty patients were identified including 2 new French cases. PIDs were varied: immunoglobulin deficits (n = 30), chronic granulomatous disease (n = 3), hyper-IgM syndrome (n = 3), hereditary complete C4 deficiency (n = 1), leucocyte adhesion deficiency type 1 (n = 1), hyper-IgE syndrome (n = 1), and Chediak-Higashi syndrome (n = 1). The mean age at PID diagnosis was 22.2 ± 16.02 years. Renal involvement was the most common manifestation of AAA (80%). Infections were extremely heterogeneous; bacterial infection with pulmonary involvement was the most frequent. Bronchiectasis was particularly common (52.5%). The delay between the first symptoms of PID and AAA diagnosis was 16.18 ± 7 years. Thirteen concomitant diagnoses were made. Twenty patients died during follow-up.
CONCLUSION
AAA is a rare life-threatening complication of PID, especially in cases of long diagnostic and therapeutic delays. Bronchiectasis should be considered as a warning sign of chronic inflammation and increased risk of AAA.
Topics: Amyloidosis; Bronchiectasis; Humans; Immunoglobulins; Immunologic Deficiency Syndromes; Primary Immunodeficiency Diseases
PubMed: 33007500
DOI: 10.1016/j.jaip.2020.09.023 -
JAMA Jul 2020Many patients with systemic amyloidosis are underdiagnosed. Overall, 25% of patients with immunoglobulin light chain (AL) amyloidosis die within 6 months of diagnosis...
IMPORTANCE
Many patients with systemic amyloidosis are underdiagnosed. Overall, 25% of patients with immunoglobulin light chain (AL) amyloidosis die within 6 months of diagnosis and 25% of patients with amyloid transthyretin (ATTR) amyloidosis die within 24 months of diagnosis. Effective therapy exists but is ineffective if end-organ damage is severe.
OBJECTIVE
To provide evidence-based recommendations that could allow clinicians to diagnose this rare set of diseases earlier and enable accurate staging and counseling about prognosis.
EVIDENCE REVIEW
A comprehensive literature search was conducted by a reference librarian with publication dates from January 1, 2000, to December 31, 2019. Key search terms included amyloid, amyloidosis, nephrotic syndrome, heart failure preserved ejection fraction, and peripheral neuropathy. Exclusion criteria included case reports, non-English-language text, and case series of fewer than 10 patients. The authors independently selected and appraised relevant literature.
FINDINGS
There was a total of 1769 studies in the final data set. Eighty-one articles were included in this review, of which 12 were randomized clinical trials of therapy that included 3074 patients, 9 were case series, and 3 were cohort studies. The incidence of AL amyloidosis is approximately 12 cases per million persons per year and there is an estimated prevalence of 30 000 to 45 000 cases in the US and European Union. The incidence of variant ATTR amyloidosis is estimated to be 0.3 cases per year per million persons with a prevalence estimate of 5.2 cases per million persons. Wild-type ATTR is estimated to have a prevalence of 155 to 191 cases per million persons. Amyloidosis should be considered in the differential diagnosis of adult nondiabetic nephrotic syndrome; heart failure with preserved ejection fraction, particularly if restrictive features are present; unexplained hepatomegaly without imaging abnormalities; peripheral neuropathy with distal sensory symptoms, such as numbness, paresthesia, and dysesthesias (although the autonomic manifestations occasionally may be the presenting feature); and monoclonal gammopathy of undetermined significance with atypical clinical features. Staging can be performed using blood testing only. Therapeutic decision-making for AL amyloidosis involves choosing between high-dose chemotherapy and stem cell transplant or bortezomib-based chemotherapy. There are 3 therapies approved by the US Food and Drug Administration for managing ATTR amyloidosis, depending on clinical phenotype.
CONCLUSIONS AND RELEVANCE
All forms of amyloidosis are underdiagnosed. All forms now have approved therapies that have been demonstrated to improve either survival or disability and quality of life. The diagnosis should be considered in patients that have a multisystem disorder involving the heart, kidney, liver, or nervous system.
Topics: Algorithms; Benzoxazoles; Dexamethasone; Diagnosis, Differential; Gene Silencing; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Liver Transplantation; Melphalan; Prognosis; Proteinuria; Stem Cell Transplantation
PubMed: 32633805
DOI: 10.1001/jama.2020.5493 -
JACC. Cardiovascular Imaging Jun 2020This study aimed to compare the diagnostic and prognostic performance of native T1 mapping (T1), extracellular volume (ECV) mapping, and late gadolinium enhancement... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
This study aimed to compare the diagnostic and prognostic performance of native T1 mapping (T1), extracellular volume (ECV) mapping, and late gadolinium enhancement (LGE) imaging for evaluating cardiac amyloidosis (CA).
BACKGROUND
CA is a progressive infiltrative process in the extracellular space that is often underdiagnosed and holds a poor prognosis. Cardiac magnetic resonance (CMR) offers novel techniques for detecting and quantifying the disease burden of CA.
METHODS
We searched PubMed for published studies using native T1, ECV, or LGE to diagnose and prognosticate CA. A total of 18 diagnostic (n = 2,015) and 13 prognostic studies (n = 1,483) were included for analysis. Pooled sensitivities, specificities, diagnostic odds ratios (DORs) of all diagnostic tests were assessed by bivariate analysis. Pooled hazard ratios (HRs) for mortality for the 3 techniques were determined.
RESULTS
Bivariate comparison showed that ECV (DOR: 84.6; 95% confidence interval [CI]: 30.3 to 236.2) had a significantly higher DOR for CA than LGE (DOR: 20.1; 95% CI: 9.1 to 44.1; p = 0.03 vs. ECV). There was no significant difference between LGE and native T1 for sensitivity, specificity, and DOR. HR was significantly higher for ECV (HR: 4.27; 95% CI: 2.87 to 6.37) compared with LGE (HR: 2.60; 95% CI: 1.90 to 3.56; p = 0.03 vs. ECV) and native T1 (HR: 2.04; 95% CI: 1.24 to 3.37; p = 0.01 vs. ECV).
CONCLUSIONS
ECV demonstrates a higher diagnostic OR for assessing cardiac amyloid than LGE and a higher HR for adverse events compared with LGE and native T1. In addition, native T1 showed similar sensitivity and specificity as ECV and LGE without requiring contrast material. Although limited by study heterogeneity, this meta-analysis suggests that ECV provides high diagnostic and prognostic utility for the assessment of cardiac amyloidosis.
Topics: Adult; Aged; Amyloid Neuropathies, Familial; Cardiomyopathies; Female; Gadolinium; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Male; Middle Aged; Myocardium; Predictive Value of Tests; Reproducibility of Results; Stroke Volume; Ventricular Function, Left
PubMed: 32498919
DOI: 10.1016/j.jcmg.2020.03.010 -
The Cochrane Database of Systematic... Apr 2020Disease-modifying pharmacological agents for transthyretin (TTR)-related familial amyloid polyneuropathy (FAP) have become available in the last decade, but evidence on...
BACKGROUND
Disease-modifying pharmacological agents for transthyretin (TTR)-related familial amyloid polyneuropathy (FAP) have become available in the last decade, but evidence on their efficacy and safety is limited. This review focuses on disease-modifying pharmacological treatment for TTR-related and other FAPs, encompassing amyloid kinetic stabilisers, amyloid matrix solvents, and amyloid precursor inhibitors.
OBJECTIVES
To assess and compare the efficacy, acceptability, and tolerability of disease-modifying pharmacological agents for familial amyloid polyneuropathies (FAPs).
SEARCH METHODS
On 18 November 2019, we searched the Cochrane Neuromuscular Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, and Embase. We reviewed reference lists of articles and textbooks on peripheral neuropathies. We also contacted experts in the field. We searched clinical trials registries and manufacturers' websites.
SELECTION CRITERIA
We included randomised clinical trials (RCTs) or quasi-RCTs investigating any disease-modifying pharmacological agent in adults with FAPs. Disability due to FAP progression was the primary outcome. Secondary outcomes were severity of peripheral neuropathy, change in modified body mass index (mBMI), quality of life, severity of depression, mortality, and adverse events during the trial.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methodology.
MAIN RESULTS
The review included four RCTs involving 655 people with TTR-FAP. The manufacturers of the drugs under investigation funded three of the studies. The trials investigated different drugs versus placebo and we did not conduct a meta-analysis. One RCT compared tafamidis with placebo in early-stage TTR-FAP (128 randomised participants). The trial did not explore our predetermined disability outcome measures. After 18 months, tafamidis might reduce progression of peripheral neuropathy slightly more than placebo (Neuropathy Impairment Score (NIS) in the lower limbs; mean difference (MD) -3.21 points, 95% confidential interval (CI) -5.63 to -0.79; P = 0.009; low-certainty evidence). However, tafamidis might lead to little or no difference in the change of quality of life between groups (Norfolk Quality of Life-Diabetic Neuropathy (Norfolk QOL-DN) total score; MD -4.50 points, 95% CI -11.27 to 2.27; P = 0.19; very low-certainty evidence). No clear between-group difference was found in the numbers of participants who died (risk ratio (RR) 0.65, 95% CI 0.11 to 3.74; P = 0.63; very low-certainty evidence), who dropped out due to adverse events (RR 1.29, 95% CI 0.30 to 5.54; P = 0.73; very low-certainty evidence), or who experienced at least one severe adverse event during the trial (RR 1.16, 95% CI 0.37 to 3.62; P = 0.79; very low-certainty evidence). One RCT compared diflunisal with placebo (130 randomised participants). At month 24, diflunisal might reduce progression of disability (Kumamoto Score; MD -4.90 points, 95% CI -7.89 to -1.91; P = 0.002; low-certainty evidence) and peripheral neuropathy (NIS plus 7 nerve tests; MD -18.10 points, 95% CI -26.03 to -10.17; P < 0.001; low-certainty evidence) more than placebo. After 24 months, changes from baseline in the quality of life measured by the 36-Item Short-Form Health Survey score showed no clear difference between groups for the physical component (MD 6.10 points, 95% CI 2.56 to 9.64; P = 0.001; very low-certainty evidence) and the mental component (MD 4.40 points, 95% CI -0.19 to 8.99; P = 0.063; very low-certainty evidence). There was no clear between-group difference in the number of people who died (RR 0.46, 95% CI 0.15 to 1.41; P = 0.17; very low-certainty evidence), in the number of dropouts due to adverse events (RR 2.06, 95% CI 0.39 to 10.87; P = 0.39; very low-certainty evidence), and in the number of people who experienced at least one severe adverse event (RR 0.77, 95% CI 0.18 to 3.32; P = 0.73; very low-certainty evidence) during the trial. One RCT compared patisiran with placebo (225 randomised participants). After 18 months, patisiran reduced both progression of disability (Rasch-built Overall Disability Scale; least-squares MD 8.90 points, 95% CI 7.00 to 10.80; P < 0.001; moderate-certainty evidence) and peripheral neuropathy (modified NIS plus 7 nerve tests - Alnylam version; least-squares MD -33.99 points, 95% CI -39.86 to -28.13; P < 0.001; moderate-certainty evidence) more than placebo. At month 18, the change in quality of life between groups favoured patisiran (Norfolk QOL-DN total score; least-squares MD -21.10 points, 95% CI -27.20 to -15.00; P < 0.001; low-certainty evidence). There was little or no between-group difference in the number of participants who died (RR 0.61, 95% CI 0.21 to 1.74; P = 0.35; low-certainty evidence), dropped out due to adverse events (RR 0.33, 95% CI 0.13 to 0.82; P = 0.017; low-certainty evidence), or experienced at least one severe adverse event (RR 0.91, 95% CI 0.64 to 1.28; P = 0.58; low-certainty evidence) during the trial. One RCT compared inotersen with placebo (172 randomised participants). The trial did not explore our predetermined disability outcome measures. From baseline to week 66, inotersen reduced progression of peripheral neuropathy more than placebo (modified NIS plus 7 nerve tests - Ionis version; MD -19.73 points, 95% CI -26.50 to -12.96; P < 0.001; moderate-certainty evidence). At week 65, the change in quality of life between groups favoured inotersen (Norfolk QOL-DN total score; MD -10.85 points, 95% CI -17.25 to -4.45; P < 0.001; low-certainty evidence). Inotersen may slightly increase mortality (RR 5.94, 95% CI 0.33 to 105.60; P = 0.22; low-certainty evidence) and occurrence of severe adverse events (RR 1.48, 95% CI 0.85 to 2.57; P = 0.16; low-certainty evidence) compared to placebo. More dropouts due to adverse events were observed in the inotersen than in the placebo group (RR 8.57, 95% CI 1.16 to 63.07; P = 0.035; low-certainty evidence). There were no studies addressing apolipoprotein AI-FAP, gelsolin-FAP, and beta-2-microglobulin-FAP.
AUTHORS' CONCLUSIONS
Evidence on the pharmacological treatment of FAPs from RCTs is limited to TTR-FAP. No studies directly compare disease-modifying pharmacological treatments for TTR-FAP. Results from placebo-controlled trials indicate that tafamidis, diflunisal, patisiran, and inotersen may be beneficial in TTR-FAP, but further investigations are needed. Since direct comparative studies for TTR-FAP will be hampered by sample size and costs required to demonstrate superiority of one drug over another, long-term non-randomised open-label studies monitoring their efficacy and safety are needed.
Topics: Amyloid Neuropathies, Familial; Benzoxazoles; Diflunisal; Disease Progression; Humans; Oligonucleotides; Patient Dropouts; Quality of Life; RNA, Small Interfering; Randomized Controlled Trials as Topic
PubMed: 32311072
DOI: 10.1002/14651858.CD012395.pub2 -
Frontiers in Pharmacology 2019The present Bayesian network meta-analysis (NMA) was to compare the efficacy of different chemotherapies and autologous stem cell transplantation (ASCT) in...
BACKGROUND/AIMS
The present Bayesian network meta-analysis (NMA) was to compare the efficacy of different chemotherapies and autologous stem cell transplantation (ASCT) in immunoglobulin light-chain (AL) amyloidosis.
METHODS
We systematically searched PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials (CENTRAL) for studies compared the rates of hematological response (HR), complete response (CR), renal response, and cardiac response in AL amyloidosis patients.
RESULTS
There were three randomized controlled trials (RCTs) and thirteen observational controlled trials (OCTs) comprising 3,402 participants enrolled for the comparisons of seven treatments: melphalan + dexamethasone (MDex), high-dose melphalan followed by ASCT, bortezomib + melphalan + dexamethasone (BMDex), thalidomide + cyclophosphamide + dexamethasone (CTD), bortezomib + dexamethasone (BDex), bortezomib + cyclophosphamide + dexamethasone (CyBorD), cyclophosphamide + lenalidomide + dexamethasone (CLD). BMDex was ranked first in the aspect of both HR and CR, CTD induced the highest rate of renal response, and BDex was possibly the best treatment for the cardiac response.
CONCLUSION
Although more data about safety and cost are needed, BMDex was recommended as the most efficient treatment for AL amyloidosis patients for enhancing the response rate for HR and CR.
PubMed: 32063846
DOI: 10.3389/fphar.2019.01601 -
Autoimmunity Reviews Feb 2020To evaluate the prevalence, clinical presentation, serological and morphological features of, and therapeutic options for Interstitial Lung Disease (ILD) in primary...
Clinical, morphological features and prognostic factors associated with interstitial lung disease in primary Sjӧgren's syndrome: A systematic review from the Italian Society of Rheumatology.
OBJECTIVE
To evaluate the prevalence, clinical presentation, serological and morphological features of, and therapeutic options for Interstitial Lung Disease (ILD) in primary Sjögren's Syndrome (pSS).
METHODS
Pubmed was searched between February 1996 and December 2018 using a combination of MESH terms related to pSS and ILD. Selected works were subjected to blind evaluation by two authors and a senior author in case of disagreement. The work followed PRISMA guidelines and was registered on PROSPERO (CRD42018118669).
RESULTS
About 20% of pSS patients have ILD, with a 5-y survival of 84% and a need for supplemental oxygen in the 11-33% range. A significant proportion of ILD patients are seronegative without sicca syndrome. ILD seems to be associated with higher levels of Lactic Dehydrogenases and positivity for Anti-Ro52k. The prevalent pattern in High Resolution Computed Tomography is Nonspecific Interstitial Pneumonia (NSIP), but all other patterns can be present. No difference in mortality was found between patients with NSIP and Usual Interstitial Pneumonia patterns. Amyloidosis and primary lung lymphoma can be observed in about 10% of pSS patients.
CONCLUSION
The recognition of pSS underlying an ILD can be challenging in seronegative patients with no or mild sicca symptoms. A complete diagnostic assessment, including minor salivary glands and, in some cases, lung biopsy, should be performed on all patients at risk. A better recognition of the clinical or serological markers of ILD progression in these patients is warranted to drive the physicians to an early diagnosis and an effective treatment.
Topics: Humans; Italy; Lung Diseases, Interstitial; Prognosis; Rheumatology; Sjogren's Syndrome; Societies, Medical
PubMed: 31843713
DOI: 10.1016/j.autrev.2019.102447 -
ESC Heart Failure Oct 2019The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and... (Comparative Study)
Comparative Study Meta-Analysis
AIMS
The study aims to systematically assess the diagnostic performance of cardiac magnetic resonance (CMR) and nuclear scintigraphy (index tests) for the diagnosis and differentiation of subtypes of cardiac amyloidosis.
METHODS AND RESULTS
MEDLINE and Embase electronic databases were searched for studies evaluating the diagnostic performance of CMR or nuclear scintigraphy in detecting cardiac amyloidosis and subsequently in differentiating transthyretin amyloidosis (ATTR) from immunoglobulin light-chain (AL) amyloidosis. In this meta-analysis, histopathological examination of tissue from endomyocardial biopsy (EMB) or extra-cardiac organs were reference standards. Pooled sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio were calculated, and a random effects meta-analysis was used to estimate diagnostic odds ratios. Methodological quality was assessed using a validated instrument. Of the 2947 studies identified, 27 met the criteria for inclusion. Sensitivity and specificity of CMR in diagnosing cardiac amyloidosis was 85.7% and 92.0% against EMB reference and 78.9% and 93.9% with any organ histology reference. Corresponding sensitivity and specificity of nuclear scintigraphy was 88.4% and 87.2% against EMB reference and 82.0% and 98.8% with histology from any organ. CMR was unable to reliably differentiate ATTR from AL amyloidosis (sensitivity 28.1-99.0% and specificity 11.0-60.0%). Sensitivity and specificity of nuclear scintigraphy in the differentiation of ATTR from AL amyloidosis ranged from 90.9% to 91.5% and from 88.6% to 97.1%. Pooled negative likelihood ratio and positive likelihood ratio for scintigraphy in this setting were 0.1 and 8, with EMB reference standard. Study quality assessed by QUADAS-2 was generally poor with evidence of bias.
CONCLUSIONS
Cardiac magnetic resonance is a useful test for diagnosing cardiac amyloidosis but is not reliable in further classifying the disease. Nuclear scintigraphy offers strong diagnostic performance in both the detection of cardiac amyloidosis and differentiating ATTR from AL amyloidosis. Our findings support the use of both imaging modalities in a non-invasive diagnostic algorithm that also tests for the presence of monoclonal protein.
Topics: Amyloid Neuropathies, Familial; Amyloidosis; Biopsy; Diagnosis, Differential; Heart Diseases; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Prevalence; Radionuclide Imaging; Sensitivity and Specificity
PubMed: 31487121
DOI: 10.1002/ehf2.12511 -
European Journal of Internal Medicine Nov 2019The role of bortezomib in the treatment of immunoglobulin light chain (AL) amyloidosis is not well defined. We performed this meta-analysis to evaluate the efficacy and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The role of bortezomib in the treatment of immunoglobulin light chain (AL) amyloidosis is not well defined. We performed this meta-analysis to evaluate the efficacy and safety of bortezomib-based regimens in patients with AL amyloidosis who are not eligible for or refuse autologous stem cell transplantation.
METHODS
A systematic search of Medline, Embase, and the Cochrane Library was conducted to identify related studies.
RESULTS
Twenty-four studies with 1238 patients were included. The pooled overall response rate (ORR) and complete hematological response rate (CHR) were 0.72 (95% CI, 0.67-0.77) and 0.35 (95% CI, 0.30-0.40), respectively. Bortezomib significantly improved the outcome of ORR compared to other regimens (RR 1.28, 95% CI, 1.04-1.57, P = .02). Similar results were observed in CHR (RR 1.90, 95% CI, 1.45-2.50, P < .001) and cardiac response (RR 2.03, 95% CI, 1.31-3.13, P = .002), but not in overall survival (HR 0.82, 95% CI, 0.62-1.09, P = .17). In addition, once-weekly bortezomib was associated with improved overall survival compared with twice-weekly bortezomib (HR 0.52, 95% CI, 0.27-0.99, P = .05). Peripheral neuropathy was the most widely reported adverse event. Incorporation of bortezomib into the standard melphalan + dexamethasone setting showed a trend of increased serious adverse events, though this was not statistically significant (RR 1.29, 95% CI, 0.95-1.75, P = .10).
CONCLUSIONS
Current evidence indicates that bortezomib-based regimens might be effective and safe therapies for patients with AL amyloidosis. There is a great need to conduct more well-designed randomized controlled trials to provide high-quality evidence.
Topics: Antineoplastic Agents; Bortezomib; Humans; Immunoglobulin Light-chain Amyloidosis; Treatment Outcome
PubMed: 31447275
DOI: 10.1016/j.ejim.2019.08.011 -
Amyloid : the International Journal of... 2019
Topics: Aged; Amyloidosis; Heart Failure; Humans; Immunoglobulin Heavy Chains; Immunoglobulin Light Chains; Male; Nephrotic Syndrome
PubMed: 31343287
DOI: 10.1080/13506129.2019.1582022 -
Journal of Lower Genital Tract Disease Jul 2019The aim of the study was to review uncommon foreskin dermatopathology conditions clinically and pathologically.
OBJECTIVES
The aim of the study was to review uncommon foreskin dermatopathology conditions clinically and pathologically.
METHODS
A database search of PubMed and Google Scholar were extracted between March 1, 2009, and March 1, 2019, using the search terms "foreskin," "prepuce," "penis," "pathology," "dermatology," and "rare." The search was limited to "humans" and "dermatopathology." Full article texts were reviewed. Reference lists were screened for additional articles. Patient details (diagnosis, dermatopathology, treatment, and follow-up if available) were extracted. We excluded articles written in the non-English language, unusual variants of common conditions, and cases of common dermatologic conditions.
RESULTS
A list of 369 articles was identified and another screening identified 30 articles for rare foreskin pathologies. Those are divided into categories based on the following etiologies: (a) benign, including congenital (e.g., aposthia), infectious (graft versus host disease and histoplasma), autoimmune (Crohn's disease and pyoderma gangrenosum), and benign neoplasms (neurofibroma, apocrine hidrocystoma, verruciform xanthoma, porokeratosis, penile cutaneous horn, localized amyloidosis) and (b) malignancies, including primary (myeloid sarcoma, basal cell carcinoma, Kaposi's sarcoma, mucosal-associated lymphoid tissue lymphoma), and metastasis.
CONCLUSIONS
We reviewed and discussed unusual benign and malignant dermatopathology conditions that can affect the foreskin.
Topics: Adult; Aged; Autoimmune Diseases; Child; Child, Preschool; Dermatitis; Foreskin; Humans; Male; Middle Aged; Neoplasms; Penile Neoplasms
PubMed: 31149956
DOI: 10.1097/LGT.0000000000000478