Treatment of Bullous Pemphigoid With Dupilumab: A Case Series of 30 Patients.

Bullous pemphigoid is often difficult to treat with the limited therapies available. Here, we describe clinical outcomes among 30 adults with bullous pemphigoid patients treated with dupilumab. We performed a multicenter, retrospective case series between March 2020 to August 2022. Patients received a loading dose of dupilumab 600 mg, followed by 300 mg maintenance dose with varying administration frequency tailored to individual patient response. All patients experienced at least some improvement in blister formation and pruritus, with 23 (76.7%) of patients demonstrating either complete clearance of blistering or marked response. Complete clearance of pruritus or marked response was noted in 25 (83.3%) of patients. Eight patients were effectively maintained solely on dupilumab. One (3.3%) patient reported an injection site reaction. Thirty patients represent a small sample, however, to our knowledge, this is the second largest group of BP treated with dupilumab. Furthermore, we provide an understandable framework for clinicians outside of academics to follow and assess treatment responses in their BP patients treated with dupilumab. Dupilumab should be considered as a therapeutic option in patients with bullous pemphigoid given its ability to induce sustained blistering and pruritus response in both typical and refractory cases while maintaining a favorable safety profile. J Drugs Dermatol. 2024;23(6):e144-e148. doi:10.36849/JDD.8258e.

Respiratory alkalosis may impair the production of vitamin D and lead to significant morbidity, including the fibromyalgia syndrome.

Hyperventilation caused by physical and/or psychological stress may lead to significant respiratory alkalosis and an elevated systemic pH. The alkalotic pH may in turn suppress the normal renal release of phosphate into the urine, thereby interrupting the endogenous production of 1,25-dihydroxyvitamin D (calcitriol). This could cause a shortfall in its normal production, leading to a variety of adverse consequences. It might partially explain the pathogenesis of acute mountain sickness, a treatable disease characterized by severe hyperventilation secondary to the hypoxia of high altitude exposure. Milder degrees of hyperventilation due to different forms of stress may produce other conditions which share characteristics with acute mountain sickness. One of these may be the fibromyalgia syndrome, a chronic painful disorder for which no satisfactory treatment exists. Should fibromyalgia and acute mountain sickness have a common etiology, may they also share a common form of treatment? Evidence is presented to support this hypothesis.

Origins and consequences of the elongation of the human menstrual cycle during the menopausal transition: the FREEDOM Study.

The menopausal transition is characterized by the appearance of elongated cycles, which become longer and more frequent as menopause approaches. Several endocrine abnormalities have been attributed to these cycles; however, no quantitative studies of their causes and consequences exist to date. This study is based on sequential daily urinary concentrations of FSH, LH, estrone 3-glucuronide (E1G), and pregnanediol 3-glucuronide (PdG) from 34 women with perimenopausal menstrual irregularity (total of 289 cycles). The timing of ovarian response was determined as the day of E1G take-off (ETO). Other parameters measured were the mean FSH concentration before ETO (FSH(ETO)) and the midluteal levels of PdG, E1G, and LH. There was a strong parallelism between ETO and cycle length variability. FSH(ETO) levels increased gradually with ETO. Both ETO and FSH(ETO) were inversely related to luteal PdG and directly related to E1G. PdG and LH levels were inversely related. All comparisons were highly significant (P < 0.0001). We conclude that delayed ovarian response underlies the elongation of the menstrual cycle in the menopausal transition, which is likely to be caused by a temporary lack of ovarian responsiveness to FSH. A progressive decline in luteal PdG with increased E1G occurs in association with these trends.

Relationship between follicle-stimulating hormone levels at the beginning of the human menstrual cycle, length of the follicular phase and excreted estrogens: the FREEDOM study.

Although reproductive aging has been separately related to elevated FSH and shorter follicular phase (FP), the direct association between both parameters has not been investigated. Also, the exact effects of increased FSH on estrogen production are yet to be established.A large database of daily urinary concentrations of FSH, LH, and estrone 3-glucuronide (E1G) from 37 regularly menstruating women (median 11 cycles per patient) was used. Initial FSH levels (iFSH) were estimated as the mean value of d 1-5. The day of E1G take-off (ETO) was determined by an algorithm, and accordingly, the FP was divided into early (d 1 to ETO) and late (ETO+1 to LH peak). FP maximum and integrated E1G were calculated. Subjects were distributed according to their mean iFSH into three categories (5 to 10, and >10 IU/liter). There was a gradual decrease in FP length with increasing category (15.2 +/- 3.8, 14.1 +/- 3.6, and 13 +/- 2.6 d, respectively; P < 0.0001). A similar effect occurred in early FP (7.5 +/- 4, 6.4 +/- 3.7, and 5.4 +/- 2.7; P < 0.0001); in contrast, late FP was unaffected (7.7 +/- 2.1, 7.7 +/- 2.1, and 7.6 +/- 2.4; P = 0.86). No consistent increase in E1G was found with advancing iFSH category; however, women with mean initial LH higher than 6 IU/liter had significantly elevated maximum (P < 0.0001) and integrated (P = 0.002) E1G.FP length decreases in parallel with increasing iFSH, with a selective effect on the early FP. Increased FSH does not affect E1G; however, elevated initial LH level was related to higher E1G.

Urinary hormone levels during the natural menstrual cycle: the effect of age.

A number of studies have identified hormonal changes in women during their reproductive lifespan, many focusing upon changes in women over the age of 40 years. The present study has determined the effect of increasing age on hormone levels over three decades. Daily early morning urine samples were assayed for estrone-3-glucuronide (E3 G), pregnanediol-3-glucuronide (P3 G), testosterone-17-glucuronide (T17 G), FSH and LH. An examination of the validity of using creatinine as a volume adjuster in urine samples formed an integral part of the analysis. Volunteers were healthy women who had regular (25-35 days) cycles, were not taking oral contraceptives, hormone therapies or any other medication. Three age groups were compared: 20-29 years (n=13), 30-39 years (n=9) and 40-49 years (n=13). Statistical analyses were carried out using two-way ANOVA and post hoc t-tests. Creatinine excretion, despite revealing no cycle-related variation in any age group, showed a decline with increasing age. Creatinine output was significantly lower in the 40-49 years age group in all phases of the cycle than in the 20-29 and 30-39 groups (P<0.0001). Uncorrected levels of E3 G were significantly higher in the 30-39 years group when compared with the 40-49 age group (P<0.0001). Uncorrected P3 G output was significantly higher in women aged 20-29 years than in women aged 40-49 years (P<0.001) and levels of uncorrected T17 G were higher in the 20-29 year age group when compared with the 30-39 or 40-49 years age group (P<0.0001). The present study is consistent with previous reports that have revealed a decline in creatinine clearance with increasing age, and therefore casts into some doubt the validity of using creatinine clearance as a procedure to correct for volume fluctuations in differing age groups of women. The study also demonstrates unequivocally that age-related variations in hormone levels are not restricted to women over 40 years of age. The novel finding of highly significant differences in mean levels of T17 G between the age groups is of considerable interest. It is presently unclear whether this resulted from specifically increased ovarian and/or adrenal secretion. The possible impacts of changes in testosterone levels during the female reproductive lifespan merits further study.

Monoclonal antibodies against progesterone: effect of steroid-carrier coupling position on antibody specificity.

Monoclonal anti-progesterone antibodies were raised by immunizing mice with progesterone coupled through either the C3, C6 or C11 positions to protein carrier (bovine serum albumin, BSA). The specificity of four antibodies for a range of steroids related to progesterone, some carrying substitutions at various ring positions, was studied by competitive inhibition in an ELISA system. The results demonstrated that the ring coupling position has a determining effect on the cross-reactivity of the antibodies obtained. The patterns of cross-reaction were interpreted in the light of the structure of the combining site of an anti-progesterone antibody (DB3) recently determined by X-ray crystallography, and inferences drawn about the orientation of steroid in the combining sites of the antibodies studied. Specifically, in two antibodies raised against progesterone-11-BSA, the orientation of steroid resembled that of the progesterone-DB3 complex, with positions C11 and C3 exposed and C6 and C20 buried; an antibody raised against progesterone-6-BSA bound steroid in an apparently similar disposition, except that C6 was exposed and C11 buried; finally, in an antibody raised against progesterone-3-BSA, all steroid positions other than C3 were apparently buried in the steroid-antibody complex.

Validations of time-resolved fluoroimmunoassays for urinary estrone 3-glucuronide and pregnanediol 3-glucuronide.

Competitive time-resolved fluoroimmunoassays (FIAs) were developed for measuring 1,3,5(10)-estratrien-3-ol-17-one glucosiduronate (estrone 3-glucuronide, E(1)3G) and 5 beta-Pregnane-3 alpha,20 alpha-diol 3-glucosiduronate (pregnanediol 3-glucuronide, Pd3G) in unextracted urine. The assays are specific, detect 0.98 ng E(1)3G/mL and 0.035 microgram Pd3G/mL, measure 102.8 +/- 2.0% of E(1)3G and 93.6 +/- 2.9% of Pd3G added, and exhibit between and within assay coefficients of variation, respectively, of 5.3% and 7.1% for E(1)3G and 6.8% and 7.8% for Pd3G. The urine matrix does not interfere with the assay. Urinary steroid glucuronide profiles measured by these FIAs conform to those of urinary steroid glucuronides and serum estradiol and progesterone measured by other established immunoassays. These FIAs afford the advantages of non-radioisotopic procedures and urine sample collection (convenience, non-invasiveness, integration of pulsatile secretion) to evaluate menstrual function in epidemiological, medical, and athletic populations.

HIV status and sociodemographic correlates of maternal body size and wasting during pregnancy.

OBJECTIVE: To examine HIV status and sociodemographic variables as correlates of body size (height, body mass index (BMI), and mid-upper-arm circumference (MUAC)) and wasting (MUAC <22 cm) in pregnant women. DESIGN: Cross-sectional study. SETTING: Four antenatal clinics in Dar es Salaam, Tanzania. SUBJECTS: Women presenting for first prenatal visit before the 23rd week of gestation, between April 1995 and July 1997 (n=13 760). RESULTS: Mean MUAC, BMI and height were 25.5 cm, 23.5 kg/m(2) and 155.1 cm, respectively. The prevalence of HIV infection was 13.1% and the overall prevalence of wasting was 4.7%. Wasting was 34% (95% CI=3%, 73%) more prevalent among HIV-infected than in uninfected mothers, after adjusting for week of gestation, height and sociodemographic indicators. The risk of wasting associated with HIV infection was highest among women with low level of education or unable to contribute to the household income. From a multiple linear regression model, BMI was positively associated with mother's age, level of education and money spent on food, but not with HIV infection, after adjusting for week of gestation. In multivariate analysis, height increased monotonically by categories of maternal age and level of education, and was also positively correlated with the ability to contribute to household income, the amount of money spent on food per person per day, and having a professional partner. CONCLUSION: HIV infection is a significant risk factor for wasting among pregnant women, particularly in groups of low socioeconomic status (SES). SES indicators are strongly correlated with maternal height and with BMI during the first and second trimesters of pregnancy independently of HIV status. SPONSORSHIP: The National Institute of Child Health and Human Development (NICHD R01 32257), and the Fogarty International Center (NIH D43 TW00004).

Expertise and category-based induction.

The authors examined inductive reasoning among experts in a domain. Three types of tree experts (landscapers, taxonomists, and parks maintenance personnel) completed 3 reasoning tasks. In Experiment 1, participants inferred which of 2 novel diseases would affect "more other kinds of trees" and provided justifications for their choices. In Experiment 2, the authors used modified instructions and asked which disease would be more likely to affect "all trees." In Experiment 3, the conclusion category was eliminated altogether, and participants were asked to generate a list of other affected trees. Among these populations, typicality and diversity effects were weak to nonexistent. Instead, experts' reasoning was influenced by "local" coverage (extension of the property to members of the same folk family) and causal-ecological factors. The authors concluded that domain knowledge leads to the use of a variety of reasoning strategies not captured by current models of category-based induction.

Extraction and purification of lipoteichoic acids from Gram-positive bacteria.

Hot and cold, 80% aqueous phenol extraction procedures together with an aqueous extraction technique have been evaluated for the isolation of lipoteichoic acids from the cytoplasmic membrane of Gram-positive bacteria. Lipoteichoic acids of Staphlococcus aureus H, Micrococcus 2102, Baccillus subtilis 168, and Bacillus subtilis W-23 were examined as each of them emphasises a different problem of contamination. The purity of the lipoteichoic acids with respect to cell-wall material, nucleic acid, and protein is discussed together with the criteria of purity which enables critical structural analysis of lipoteichoic acids to be carried out.

Association of conventional and exertional coronary heart disease risk factors in 5,000 apparently healthy men.

BACKGROUND AND HYPOTHESIS: The aim of this study was to define the prevalence of previously undetected coronary heart disease among asymptomatic males, aged 30-65 years, by means of resting and exercise electrocardiography in conjunction with an analysis of conventional and exertional coronary risk factors. METHODS: Between January 1985 and December 1989 we examined 5,000 clinically asymptomatic subjects. A detailed case history was obtained for each individual, followed by a complete physical examination, comprehensive blood (including lipid) profile, lung function tests, chest x-ray, a resting 12-lead electrocardiogram (ECG), and a maximal treadmill exercise ECG. Whenever possible, on-line computerized respiratory analysis (Beckman Metabolic Measurement Cart) was carried out during the exercise tests. Conventional and exertional coronary heart disease risk factors were also recorded. RESULTS: A total of 162 persons (3.2%) showed abnormal S-T segment responses during the exercise or recovery period. Of these, 92 subjects underwent further investigations: coronary angiography (79), 201thallium scanning (13), 201thallium scanning followed by coronary angiography (7). Of the 86 patients who proceeded to coronary angiography, 19 (22%) had either normal coronary artery anatomy or only insignificant disease. Among the 67 (78%) of patients with significant angiographically demonstrable disease, 26 received coronary artery bypass grafting, 7 underwent coronary angioplasty, and the remainder continued on medical management. CONCLUSIONS: These results are discussed in relation to a variety of conventional and exertional coronary risk factors.

Epitope masking and immunodominance--complications in the selection of monoclonal antibodies against HCG.

Spleen cells from Balb/c mice immunized with HCG were subjected to the normal hybridoma procedures. The resulting MCA's (from 78 clones) were evaluated in radioimmunoassay, haemagglutination and enzyme immunoassay with whole HCG. The RIA analysis was extended to include HCG subunits and intact LH. The alpha-chain of HCG was found to be strongly immunodominant, as shown by the very high frequency (46 of 78) of MCA's directed at the alpha-chain epitopes. These antibodies would bind luteinizing hormone as well as HCG. Only 1 of the 78 clones was specific for the B subunit of HCG, in RIA. This clone was later found to be positive for LH in EIA, thus making the derivation of antibodies specific for this B-epitope extremely difficult. Most MCA's were found to be applicable in the three types of assay systems (48 of 78), but some were compatible in just one or two of the systems. These differences are believed to be due to epitope masking resulting from the way in which the antigen was handled and presented in the different systems.

Risk factors for syphilis among HIV-1 infected pregnant women in Dar es Salaam, Tanzania.

This study was conducted to determine the risk factors for recent (active) syphilis among HIV-1 seropositive pregnant women (N = 1058) in Dar es Salaam, Tanzania, Recruitment of study participants (N = 1058) was done between April 1995 and June 1997 at four main prenatal clinics in Dar es Salaam city. Study subjects were interviewed to obtain information about potential risk factors, and blood and genital specimens were collected for detection of syphilis and other genital infections. The prevalence of active syphilis was 5.9%. After adjusting for other risk factors, women without their own source of income had a 50% lower risk of syphilis (OR = 0.5, 95% CI: 0.3-0.9). The risk of active syphilis was significantly increased among women with genital ulceration on examination (OR = 8.4, 95% CI: 1.5-47.7), and in those with trichomoniasis (OR = 2.2, 95% CI: 1.2-3.8). HIV-related immunodeficiency was not associated with increased risk of syphilis. These results show that syphilis and other genital infections are a major problem among HIV infected women. Prevention of syphilis and other genital infections is urgently needed in this population.