Clinical and histopathological features of adult patients with dermatomyositis and melanoma differentiation associated-5 autoantibody seropositivity status, as determined by commercially available testing: a retrospective, single-institution comparative cohort study.

BACKGROUND: Although melanoma differentiation associated (MDA)-5 autoantibodies have been widely explored in dermatomyositis (DM), most studies have relied on MDA-5 autoantibody testing performed in research settings, rather than the now-available commercial laboratory tests. AIM: To characterize the clinical and histopathological data in patients with DM and circulating MDA-5 autoantibodies, as defined by commercially available testing. METHODS: This was a retrospective review of patients with DM who underwent MDA-5 antibody testing. All available skin biopsy slides were reviewed. RESULTS: Cutaneous features more prevalent in MDA-5-positive DM included Raynaud phenomenon (RP) (P < 0.001), cutaneous ulcerations (P = 0.01), mechanic hands (P < 0.02), palmar papules (P < 0.01), oral ulcers (P = 0.024) and alopecia (P = 0.03). Joint and pulmonary involvement were more common in patients with MDA-5-positive DM (both P < 0.001) as was dysphagia (P < 0.01). Myopathy (P = 0.4) and malignancy (P = 0.34) were not statistically different between the cohorts. Vasculopathy was more common in MDA-5-positive DM (P < 0.01), while spongiosis was less common (P < 0.02). CONCLUSION: This study not only confirms some known associations between disease manifestations and MDA-5 autoantibody status, as determined by commercially available tests, but also identifies new associations, including RP and dysphagia.

In Vivo reflectance confocal microscopy of cutaneous acute graft-versus-host disease: concordance with histopathology and interobserver reproducibility of a glossary with representative images.

BACKGROUND: The reliability to non-invasively identify features of inflammatory dermatoses by reflectance confocal microscopy (RCM) remains unknown. Lack of formal training among RCM readers can result in inconsistent assessments, limiting clinical utility. Specific consensus terminology with representative images is necessary to ensure consistent feature-level interpretation among RCM readers. OBJECTIVES: (1) Develop a glossary with representative images of RCM features of cutaneous acute graft-versus-host disease (aGVHD) for consistent interpretation among observers, (2) assess the interobserver reproducibility among RCM readers using the glossary, and (3) determine the concordance between RCM and histopathology for aGVHD features. METHODS: Through an iterative process of refinement and discussion among five international RCM experts, we developed a glossary with representative images of RCM features of aGVHD. From April to November 2018, patients suspected of aGVHD were imaged with RCM and subsequently biopsied. 17 lesions from 12 patients had clinically and pathologically confirmed cutaneous aGVHD. For each of these lesions, four dermatopathologists and four RCM readers independently evaluated the presence of aGVHD features in scanned histopathology slides and 1.5 × 1.5 mm RCM submosaics at 4 depths (blockstacks) respectively. RCM cases were adjudicated by a fifth RCM expert. Interobserver reproducibility was calculated by mean pairwise difference (U statistic). Concordance between modalities was determined by fraction of assignments with agreement. RESULTS: We present a glossary with representative images of 18 aGVHD features by RCM. The average interobserver reproducibility among RCM readers (75%, confidence interval, CI: 71-79%) did not differ significantly from dermatopathologists (80%, 76-85%). The concordance between RCM and histopathology was 59%. CONCLUSIONS: By using the glossary, the interobserver reproducibility among RCM readers was similar to the interobserver reproducibility among dermatopathologists. There was reasonable concordance between RCM and histopathology to visualize aGVHD features. The implementation of RCM can now be advanced in a variety of inflammatory conditions with a validated glossary and representative image set.

Reactive granulomatous dermatitis as a clinically relevant and unifying term: a retrospective review of clinical features, associated systemic diseases, histopathology and treatment for a series of 65 patients at Mayo Clinic.

BACKGROUND: Reactive granulomatous dermatitis (RGD) is an umbrella term used to describe interstitial granulomatous dermatitis (IGD), palisaded neutrophilic and granulomatous dermatitis (PNGD), and interstitial granulomatous drug eruption (IGDR). OBJECTIVE: The aim of this study was to describe systemic associations of RGD, explore possible associations between histopathologic findings and systemic RGD associations and determine clinical relevance of RGD subtypes. METHODS: We retrospectively studied clinical and histopathologic characteristics of patients with RGD from 1990 through 2020. RESULTS: Of 65 patients with RGD (41 women, 24 men; median age at diagnosis, 62 years), 37 had IGD, 26 had PNGD, and 2 had IGDR. Fifty patients (76.9%) had an associated systemic condition; rheumatologic conditions were identified for 34 (52.3%) patients. The associated systemic condition occurred before RGD in approximately 75% of patients. Statistical analyses did not show significant associations between specific subtypes of RGD and systemic diseases or treatment response, and specific histopathologic findings were not predictive of an associated systemic disease. CONCLUSIONS: Although most patients with RGD had an associated systemic condition, subtypes of RGD did not correlate with systemic associations, lending support to the use of the umbrella term RGD.

Differential expression of interferon-induced genes and other tissue-based biomarkers in acute graft-versus-host disease vs. lupus erythematosus in skin.

BACKGROUND: In both acute graft-versus-host disease (GVHD) and lupus erythematosus (LE), the patient's own tissues are subjected to immunological assault via complex mechanisms influenced by interferon (IFN) and other cytokines. Although not typically confused clinically, these entities have overlapping histopathological findings in the skin. AIM: To assess whether GVHD can be differentiated from LE using molecular methods on skin specimens. METHODS: We developed a quantitative reverse transcription PCR assay based on previously identified tissue-based biomarkers of cutaneous GVHD, and compared gene expression in GVHD with that in LE. RESULTS: Both entities showed robust expression of IFN-induced genes and of genes encoding proteins involved in antigen presentation, cell signalling and tissue repair. Levels of gene expression differed significantly in GVHD compared with LE, particularly those of IFN-induced genes such as MX1, OAS3, TAP1 and STAT3 (P < 0.01). Three logistic regression models could differentiate the two entities with a high degree of certainty (receiver operating characteristic area under the curve of 1.0). CONCLUSION: The study demonstrates the feasibility of distinguishing between microscopically similar inflammatory dermatoses using tissue-based molecular techniques.

International Bullous Diseases Group: consensus on diagnostic criteria for epidermolysis bullosa acquisita.

BACKGROUND: Epidermolysis bullosa acquisita (EBA) is a complex autoimmune bullous disease disease with variable clinical presentations and multiple possible diagnostic tests, making an international consensus on the diagnosis of EBA essential. OBJECTIVES: To obtain an international consensus on the clinical and diagnostic criteria for EBA. METHODS: The International Bullous Diseases Group (IBDG) met three times to discuss the clinical and diagnostic criteria for EBA. For the final voting exercise, 22 experts from 14 different countries voted on 50 different items. When > 30% disagreed with a proposal, a discussion was held and re-voting carried out. RESULTS: In total, 48 of 50 proposals achieved consensus after discussion. This included nine diagnostic criteria, which are summarized in a flow chart. The IBDG was unable to determine one procedure that would be applicable worldwide. A limitation of the study is that differential diagnosis of bullous systemic lupus erythematosus has not been addressed. CONCLUSIONS: This first international consensus conference established generally agreed-upon clinical and laboratory criteria defining the clinical classification of and diagnostic testing for EBA. Holding these voting exercises in person with the possibility of discussion prior to voting has advantages in reaching consensus over Delphi exercises with remote voting.

Underreported use of palliative care and patient-reported outcome measures to address reduced quality of life in patients with calciphylaxis: a systematic review.

Calciphylaxis is associated with significant morbidity and mortality. Palliative care (PC) is a subspecialty that treats the pain and stress of serious illness. To assess whether the role of quality of life (QoL) indices, patient-reported outcome measures and PC have been studied in patients with calciphylaxis, we performed a systematic literature review. Several databases were searched from inception to October 2016 according to modified Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria. We searched for papers on calciphylaxis that mentioned the symptoms and supportive needs of patients, QoL or outcome measures to report symptom severity, and the involvement of PC. Twelve papers met the inclusion criteria. Reported patient symptoms included pain, skin lesion resolution and pruritus, with the first being the most frequently reported. Four papers measured pain using a previously verified patient-reported outcome measure, including the Visual Analogue Scale. One paper used a verified QoL measure, the Dermatology Quality of Life Index. No tool was used consistently. Eight papers reported the use of hospice care or PC in the treatment of calciphylaxis. No outcome measure was used to prompt PC involvement. Overall, QoL indices, patient-reported outcome measures and PC are underreported in the treatment of calciphylaxis. PC may be a resource to assist in symptom management and adaptive coping strategies for patients from the onset of disease.

Leukocytoclastic vasculitis in children: clinical characteristics, subtypes, causes and direct immunofluorescence findings of 56 biopsy-confirmed cases.

BACKGROUND: Leukocytoclastic vasculitis (LCV) in children is a complex group of conditions. OBJECTIVES: This study presents the demographics, clinical features, direct immunofluorescence (DIF) results and suspected aetiologies of 56 biopsy-confirmed cases of leukocytoclastic vasculitis in children. METHODS: Retrospective review of 56 children seen at Mayo Clinic in Rochester, Minnesota, from 1993 to 2013 with clinical features and cutaneous biopsy consistent with LCV. RESULTS: Twenty-seven (48%) cases were found to be due to IgA vasculitis (Henoch-Schonlein purpura). The remaining cases were found to be due to cutaneous small-vessel vasculitis (n = 19, 34%), urticarial vasculitis (n = 5, 9%), ANCA-associated vasculitis (n = 4, 7%) and acute haemorrhagic oedema of infancy (n = 1, 2%). IgA vasculitis was found to be associated with abdominal pain (P = 0.008), whereas the non-IgA vasculitis group was associated with headache (P = 0.052). Children with IgA vasculitis had palpable purpura (P = <0.001), petechia (P = 0.057), vesicles (P = 0.009) and involvement of the buttock (P = 0.004) more frequently than the non-IgA vasculitis group. On DIF, perivascular IgA was positive in IgA vasculitis compared to non-IgA vasculitis cases (P = <0.001), the other conjugates were similar between the two groups. CONCLUSION: The most common subtype of biopsy-confirmed LCV in children is IgA vasculitis. Clinical features, exam characteristics and DIF results can be helpful in determining the subtype of cutaneous vasculitis in children.

Henoch-Schönlein purpura and systemic disease in children: retrospective study of clinical findings, histopathology and direct immunofluorescence in 34 paediatric patients.

BACKGROUND: Henoch-Schönlein purpura (HSP), an IgA-mediated small vessel vasculitis, is the most common form of vasculitis in children. HSP is commonly associated with systemic involvement of the gastrointestinal tract, joints and kidneys. Renal involvement is the main cause of morbidity and mortality in HSP. OBJECTIVES: To characterize the clinical, histopathological and direct immunofluorescence (DIF) findings, and to correlate the findings with systemic disease in 34 children with HSP seen at our institution. METHODS: This was a retrospective review of paediatric patients with HSP and with available biopsy specimens seen at our institution between 1993 and 2013. RESULTS: Thirty-four paediatric patients were identified (mean age 10·7 years). Renal involvement was found in 17 (50%) patients, gastrointestinal tract involvement in 22 (65%) and joint involvement in 23 (68%). Renal involvement was significantly associated with papillary dermal oedema on histopathology (P < 0·01) and the presence of perivascular C3 on DIF (P = 0·01). The presence of lesions above the waist was significantly associated with gastrointestinal involvement (P = 0·03), as was the presence of clinically apparent oedema (P = 0·01). CONCLUSIONS: This study suggests that in children with HSP, microscopic dermal oedema and C3 on DIF may be predictive of renal involvement. Patients with clinically apparent oedema and lesions above the waist are more likely to have gastrointestinal involvement.

Evidence-based guidelines for laboratory screening for infectious diseases before initiation of systemic immunosuppressive agents in patients with autoimmune bullous dermatoses.

Autoimmune bullous dermatoses (ABD) compromise the skin's innate barrier function for preventing infection. Treating patients with ABD frequently requires systemic immunosuppressive therapy, often with multiple agents. Currently, no pretreatment infection testing guidelines are available for clinicians caring for patients with ABD. We performed a systematic literature review in other medical disciplines that use similar iatrogenic immunosuppressive medications to treat various diseases and conditions and developed infection-testing recommendations for patients with ABD before initiating immunosuppressive therapy. Assessing individual patient risk factors for latent infection and preventable communicable diseases can direct testing for select infections before starting immunosuppressive therapy. Testing patients for hepatitis B virus, hepatitis C virus, and Mycobacterium tuberculosis infection is recommended before initiating rituximab treatment.

Acute myocardial infarction in an American traveler in China.

While traveling in a rural province of the People's Republic of China, an American scientist had an acute myocardial infarction that was complicated by ventricular tachycardia and congestive heart failure. Medical personnel were rapidly mobilized, and an improvised coronary care unit was created around the patient. He survived due to the organization, training, and skill of the Chinese medical staff.

HIV infection among non-injecting drug users entering drug treatment, United States, 1989-1992. Field Services Branch.

OBJECTIVE: To describe HIV seroprevalence among non-injecting drug users (non-IDU) entering sentinel drug treatment centers in the United States. DESIGN: Anonymous, blinded (unlinked) HIV seroprevalence surveys. SETTING: Sixty-eight sentinel drug treatment centers in 37 United States metropolitan areas. PARTICIPANTS: Consecutive sample of clients admitted to sentinel drug treatment centers from January 1989 through December 1992. Of 84,617 clients, 37,633 (44.5%) had used illicit drugs but reported no injecting drug use since 1978. MAIN OUTCOME MEASURES: Center-specific, metropolitan area-specific, and national median HIV seroprevalence rates. RESULTS: National median center-specific HIV seroprevalence among non-IDU was 3.2% (range, 0-15.2%). Rates varied widely by geographic area. Median rates were highest in the northeast (5.6%; range, 0-15.2%), intermediate in the south (3.4%; range, 0.6-8.0%), and generally lower throughout the rest of the country: midwest (1.3%; range, 0-3.1%) and west (1.8%; range, 0-14.5%). When stratified by treatment center, there were few statistically significant differences in seroprevalence among African Americans, Hispanics and whites. The median rate was 3.4% among men and 2.7% among women. Rates among non-IDU were lower than among IDU attending the same drug treatment centers, but consistently higher than among heterosexual patients attending sexually transmitted disease clinics in the same metropolitan areas. CONCLUSIONS: HIV seroprevalence among non-IDU entering drug treatment is high in many metropolitan areas. HIV prevention and education efforts in drug treatment centers should target sexual as well as drug-use risk reduction for all clients.

HIV infection among homeless adults and runaway youth, United States, 1989-1992. Field Services Branch.

OBJECTIVES: Homeless persons have an increased risk of HIV infection because of a high prevalence of HIV-related risk behaviors. These include drug use, sexual contact with persons at risk for HIV infection, and the exchange of sex for drugs. The objectives of this investigation were to describe HIV seroprevalence rates in homeless adults and runaway youth. METHODS: In 1989, the Centers for Disease Control and Prevention began collaboration with state and local health departments to conduct HIV seroprevalence surveys in homeless populations. Unlinked HIV seroprevalence surveys were conducted in 16 sites; 11 provided medical services primarily to homeless adults, and five to runaway youth aged < 25 years. RESULTS: From January 1989 through December 1992, annual surveys were conducted in 16 sites in 14 cities. Site-specific seroprevalence rates ranged from 0-21.1% (median, 3.3%). Among homeless adults in three sites, rates were higher among men who had sex with other men and those who injected drugs than among persons with other risk exposures (28.9 versus 5.3%). In general, rates were higher for heterosexual men than for women and higher among African Americans than whites. In sites providing services to homeless youth, HIV seroprevalence rates ranged from 0-7.3% (median, 2.3%). CONCLUSIONS: These data indicate that HIV infection among homeless adults and runaway youth is an important public health problem. HIV prevention and treatment should be integrated into comprehensive health and medical programs serving homeless populations.

Does HIV reporting by name deter testing? MESH Study Group.

OBJECTIVE: Name-based HIV reporting is controversial in the United States because of concerns that it may deter high-risk persons from being tested. We sought to determine whether persons at risk of HIV infection knew their state's HIV reporting policy and whether they had delayed or avoided testing because of it. DESIGN: A cross-sectional anonymous survey. METHODS: We interviewed 2404 participants in one of three high-risk groups: men who have sex with men (MSM), heterosexuals attending a sexually transmitted disease (STD) clinic, and street-recruited injection drug users (IDU). Participants were asked standardized questions about their knowledge of reporting policies and reasons for having delayed or avoided testing. We recruited in eight US states: four with name-based reporting and four without; all offered anonymous testing at certain sites. RESULTS: Fewer than 25% correctly identified their state's HIV reporting policy. Over 50% stated they did not know whether their state used name-based reporting. Of the total, 480 participants (20%) had never been tested. Of these, 17% from states with name-based reporting selected concern about reporting as a reason for not testing compared with 14% from states without name-based reporting (P = 0.5). Comparing previously tested participants from states with name-based reporting to those from states without, concern about HIV reporting was given as a reason for delaying testing by 26% compared with 13% of IDU (P < 0.001), and for 26% compared with 19% of MSM (P = 0.06). CONCLUSION: Most participants did not know their state's HIV reporting policy. Name-based reporting policies were not associated with avoiding HIV testing because of worry about reporting, although they may have contributed to delays in testing among some IDU.

The association of Schistosomiasis mansoni and proteinuria in an endemic area. A preliminary report.

The association of Schistosoma mansoni infection and proteinuria was investigated by measuring quantitative urinary protein in a defined population in an endemic area in northeastern Brazil. Persons with schistosomiasis had higher mean urinary protein than those without. Two of 162 persons with schistosomiasis had clear evidence of renal disease (pathologic proteinuria, abnormal urinary sediment). These results seemed to be related neither to the intensity of S. mansoni infection as measured by fecal egg excretion nor to the presence of hepatic and splenic enlargement in schistosomiasis.

Control of schistosomiasis: report of a workshop.

Nineteen scientists, field workers, and representatives of funding agencies active in schistosomiasis research and control met in Bellagio, Italy in October 1977 to attempt to evaluate the effectiveness of current control methods and what might be accomplished with available technology. The deliberations included summaries of knowledge on the biology, transmission, and control of schistosomiasis and assessment of major control programs and methodologies. The groups concluded that in the major endemic areas considerable gains in control of schistosomiasis could be made with current technology. However, maintenance of control in most countries, and establishment of serious control programs in countries in which schistosomiasis is a less severe public health problem, would require development of less expensive modalities which would need little monitoring and possibly have benefits extending beyond schistosomiasis control.

The intensity and effects of infection with Schistosoma mansoni in a rural community in northeast Brazil.

The intensity of infection with Schistosoma mansoni and its effects were investigated in a defined population living on three contiguous fazendas (subcounties) in a nonmalarious area of northeast Brazil near Salvador, Bahia. Quantitative stool egg counts (Bell technique) were performed on 363 of 417 individuals (90%) of all ages; physical examinations were done on 294 of 357 individuals (82%) 5 years of age and older. The maximum increase in prevalence was observed between the 1- to 4- and 5- to 9-year age groups, while the maximum increase in fecal egg count occurred between 5- to 9- and 10- to 14-year age groups. Highest egg counts were observed in the 10- to 14-year age group (geometric mean of 301 eggs per ml of stool) while the maximum prevalence (100%) was in the 20- to 24-year age group. In the fazenda with the lowest quantitative egg counts the age specific prevalence rates increased more slowly than in the fazendas with higher egg counts. In the study group nearly 50% of the total fecal egg output was accounted for by 22 individuals (6%) who had a mean age of 12.6 years. Egg counts for this selected group were all over 800 eggs per ml of stool with a mean of 1,514 eggs per ml of stool. In children under 15 years of age, the frequency of hepatomegaly and splenomegaly varied directly with the egg count; further, the degree of hepatomegaly was directly correlated with increasing egg counts. No splenic enlargement was noted in children not excreting eggs. In adults, on the other hand, neither splenomegaly nor hepatomegaly could be directly related to schistosomal infection per se. In children, neither the presence of infection with S. mansoni nor its intensity was reflected by altered anthropometric measurements. In the one fazenda tested the frequency of stools positive for occult blood correlated with increasing S. mansoni egg counts.

House construction, triatomine distribution, and household distribution of seroreactivity to Trypanosoma cruzi in a rural community in northeast Brazil.

Household distribution of seroreactivity to Trypanosoma cruzi in inhabitants was analyzed in relation to house construction and the distribution of Panstrongylus megistus, the principal domestic vector of Chagas' disease in a rural area in northeast Brazil. No children residing in mud-brick houses were seroreactive to T. cruzi. The highest rates of seroreactivity occurred in residents of unplastered mud-stick houses, and were twice as high as those found in persons living in mud-brick houses or plastered mud-stick houses. Two-thirds of seroreactive children in this area resided in unplastered mud-stick houses. Over 90% of the P. megistus infestations were found in mud-stick houses. Mud-brick houses had the lowest infestation rates of P. megistus and the lowest household rates of seroreactivity to T. cruzi.

The epidemiology and household distribution of seroreactivity to Trypanosoma cruzi in a rural community in northeast Brazil.

The prevalence rates and household distribution of seroreactivity to Trypanosoma cruzi by complement fixation (CF) and indirect immunofluorescent antibody methods were determined in a population of 1,087 persons living in a rural area endemic for Chagas' disease in northeast Brazil. There was a gradual rise in the rate of seropositivity to 60% by age 20. Between ages 20 and 55 the prevalence rate remained at about 60%, but declined thereafter. The decline in the older age groups was not accompanied by a fall in geometric mean titer, suggesting that the decline might better be explained by an increased mortality among those seropositive than by a decrease in CF reactivity associated with age. There was variation in the rates of seropositivity in children among the geographic subunits, but the rates among adults were fairly uniform. Household clustering of seropositivity was demonstrated when both household size and age distribution were taken into account. The presence of a seropositive child less than 5 years of age was a good indicator of a household with a high rate of seropositivity; screening for young seropositive children might be a useful tool to locate high risk households. Seropositive children in households where the mother was seropositive but the father seronegative were significantly younger than seropositive children in households where the father was seropositive but the mother seronegative even though the age distribution and the overall rate of seropositivity in both groups of children were similar; thus, conversion to seropositivity earlier in life in children of seropositive mothers may not be due solely to increased exposure, but may indicate that the immunologic response in such children differed from that of children from seronegative mothers.

Stability of faecal egg excretion in Schistosoma mansoni infection.

Stability of Schistosoma mansoni egg excretion was studied in 23 residents of a rural endemic area in North-east Brazil where the over-all prevalence rate was 87% and the peak geometric mean egg excretion was 308 eggs/ml (Bell method) in the 10 to 14-year-old age group. Stool examinations by the Kato method were performed for three to four consecutive days each month for three consecutive months. Both raw and transformed data showed significant stability of S. mansoni egg excretion from day to day and month to month in this population. A single Kato examination detected 68% of individuals who were excreting more than 400 eggs per gramme. Although S. mansoni egg excretion is stable over time, identifying individuals with high egg excretion in endemic populations requires sensitive quantitative methods.