The overlap syndrome of urticaria and gastroesophageal reflux disease.

BACKGROUND: One-quarter of systemic symptoms associated with chronic spontaneous urticaria (CSU) are related to gastrointestinal complaints (GICs). OBJECTIVES: To investigate the prevalence and features of urticaria-overlapping GICs. METHODS: In this retrospective cross-sectional survey, 1426 consecutive outpatients were observed at our University Department. Only patients suffering from urticaria or GICs with a complete diagnostic work-up including serum total IgE level (Tot-IgE), differential blood count and urticaria activity score (UAS), were evaluated. RESULTS: Among different GICs, gastroesophageal reflux disease (GERD) was the most frequent syndrome observed (15.4%; 95%CI: 13.6-17.3). The prevalence of overlap syndrome for urticaria and GERD was 5.9% (95%CI: 4.7-7.2). In urticaria-patients, the prevalence of GERD was four-fold higher than in patients without hives (44% vs. 11%, p<0.001). UAS was significantly higher in urticaria and GERD overlap syndromes vs. isolated urticarias. In patients with GERD or acute/chronic urticaria or overlap syndrome, Tot-IgE and eosinophil blood count (EBC) differed significantly, with a stepwise increase in their values; from the subgroup of patients with GERD only, to that with overlap of CSU to GERD. Prevalence values for urticaria overlapping with GERD were three- and two-fold higher in CSU and in long-duration GERD cases respectively compared to acute urticaria or short-duration GERD cases. Similar to Th2 pathology models, CSU and GERD overlap syndrome was significantly and independently associated with Total-IgE ≥100IU/ml or EBC ≥250/mmc compared to CSU or GERD. Endoscopic/bioptic findings of non-erosive reflux disease (NERD) or Barrett's esophagus (BE) were more frequent in chronic overlap syndrome than in GERD-patients. CONCLUSIONS: GERD was the most frequent GIC in patients with urticaria. Overlap syndrome was more frequent among patients with CSU, where this syndrome was associated with higher values of UAS, Tot-IgE, EBC and frequencies of NERD and BE. These results suggest that overlap syndrome is frequently a chronic syndrome with a Th2-like profile.

Natural history of autoimmune primary ovarian insufficiency in patients with Addison's disease: from normal ovarian function to overt ovarian dysfunction.

CONTEXT: Women with autoimmune Addison's disease with normal ovulatory cycles but positive for steroid cell antibodies (StCA) have been considered at risk of premature ovarian insufficiency (POI). DESIGN: Thirty-three women younger than 40 years, with subclinical-clinical autoimmune Addison's disease but with normally ovulatory menses, were followed up for 10 years to evaluate the long-term time-related variations of StCA, ovarian function and follicular reserve. All patients and 27 control women were investigated at the start and every year for the presence and titre of StCA (by indirect immunofluorescence), serum concentrations of anti-Mullerian hormone (AMH) and ovarian function at four consecutive menses every year. RESULTS: At the start of the study StCA were present in 16 women (group 1), at low/middle titres (≤1:32) in seven of them (43.8%, group 1A), at high titres (>1:32) in the remaining nine patients (group 1B, 56.2%), while they were absent from 17 patients (group 2). During the follow-up period, all women in group 1A remained StCA-positive at low/middle titres with normal ovulatory menses and normal gonadotrophin and AMH levels, while all patients in group 1B showed a further increase of StCA titres (1:128-1:256) and progressed through three stages of ovarian function. None of the patients in group 2 and controls showed the appearance of StCA or ovarian dysfunction during the follow-up. CONCLUSIONS: The presence of StCA at high titres can be considered a good predictive marker of subsequent development of autoimmune POI. To single out the stages of autoimmune POI may allow a timely therapeutic choice in the subclinical and early clinical stages.

Longitudinal behavior of autoimmune GH deficiency: from childhood to transition age.

BACKGROUND: Some cases of apparently idiopathic GH deficiency (GHD) may be caused by pituitary autoimmunity. OBJECTIVE: To study the variations in pituitary function and antipituitary antibodies (APA) from childhood to transition age in patients with apparently idiopathic GHD. DESIGN: We conducted a longitudinal study. PATIENTS AND METHODS: Pituitary function and APA detection by immunofluorescence were investigated in 24 childhood patients with isolated GHD before starting recombinant GH therapy and after the stopping of this therapy in transition age. Sera of patients positive for APA were processed by double immunofluorescence to identify their pituitary target. RESULTS: At diagnosis, 16 out of 24 patients were APA positive targeting only somatotrophs (group 1), while the remaining eight were APA negative (group 2). When retested off therapy, 12 out of 16 patients in group 1 persisted being APA positive, while the remaining four became negative with recovery of pituitary function. All patients in group 2 persisted being APA negative but still showing GHD. Of the 12 patients persistently APA positive, eight with confirmed GHD showed APA still targeting somatotrophs, whereas four showed APA targeting only gonadotrophs associated with isolated hypogonadotropic hypogonadism (HH). CONCLUSION: Patients with APA at middle but not at high titer in childhood may show a remission of autoimmune GHD in childhood after GH replacement therapy. As APA may shift their target in transition period, an early characterization of APA by double immunofluorescence is advisable in APA positive GHD patients showing delayed puberty, to allow an early diagnosis and an appropriate therapy, thus preventing the progression toward HH.

Telaprevir may induce adverse cutaneous reactions by a T cell immune-mediated mechanism.

The HCV protease inhibitor telaprevir associated with peginterferon-alpha and ribavirin, was widely used in the recent past as standard treatment in HCV genotype-1 infected patients. Telaprevir improves the sustained virology response rates, but at the same time increases the frequency of adverse cutaneous reactions. However, mechanisms through which telaprevir induces cutaneous lesions are not yet defined. A 50-year-old woman, affected by HCV genotype 1b, was admitted to our Department for a telaprevir-related severe cutaneous eruptions, eight weeks after starting a triple therapy (telaprevir associated with Peginterferon-alpha and ribavirin). Mechanisms of cutaneous reactions were investigated by skin tests with non-irritating concentrations of telaprevir and by activating in vitro T lymphocyte with different concentrations. Immediate and delayed responses to skin testing were negative, but the drug-induced lymphocytes activation was significantly higher as compared to patient's baseline values and to parallel results obtained in three healthy subjects (p < 0.05). In conclusion, adverse cutaneous reactions of our patient were caused by a telaprevir-induced T-cell dependent immune mechanism.

Pregnancy may favour the development of severe autoimmune central diabetes insipidus in women with vasopressin cell antibodies: description of two cases.

Recently, an increased incidence of central diabetes insipidus (CDI) in pregnancy, and less frequently in the post partum period, has been reported, most probably favoured by some conditions occurring in pregnancy. This study was aimed at investigating the influence of pregnancy on a pre-existing potential/subclinical hypothalamic autoimmunity. We studied the longitudinal behaviour of arginine-vasopressin cell antibodies (AVPcAbs) and post-pituitary function in two young women with a positive history of autoimmune disease and presence of AVPcAbs, but without clinical CDI, and who became pregnant 5 and 7 months after our first observation. The behaviour of post-pituitary function and AVPcAbs (by immunofluorescence) was evaluated at baseline, during pregnancy and for 2 years after delivery. AVPcAbs, present at low/middle titres at baseline in both patients, showed a titre increase during pregnancy in one patient and after delivery in the other patient, with development of clinically overt CDI. Therapy with 1-deamino-8-d-arginine vasopressin (DDAVP) caused a prompt clinical remission. After a first unsuccessful attempt of withdrawal, the therapy was definitively stopped at the 6th and the 7th month of post partum period respectively, when AVPcAbs disappeared, accompanied by post-pituitary function recovery, persisting until the end of the follow-up. The determination of AVPcAbs is advisable in patients with autoimmune diseases planning their pregnancy, because they could be considered good predictive markers of gestational or post partum autoimmune CDI. The monitoring of AVPcAb titres and post-pituitary function during pregnancy in these patients may allow for an early diagnosis and an early replacement therapy, which could induce the disappearance of these antibodies with consequent complete remission of CDI.