Search

Abstract Background Rituximab is a monoclonal antibody inducing depletion of B lymphocytes and presently approved for the treatment of non-Hodgkin's lymphoma and rheumatoid arthritis. Here is the first report of the use of this drug in a case of Cogan's syndrome (CS). Case Presentation a 25-year-old Italian woman was referred with conjunctival hyperaemia, interstitial keratitis, moderate bilateral sensorineural hearing loss accompanied by tinnitus, dizziness, nausea and vertigo, poorly responsive to oral and topical steroidal therapy. Diagnosis of typical CS was made. The administration of a combined immunosuppressive treatment resolved ocular inflammation, dizziness, nausea, and vertigo but gave little results in controlling progressive hearing loss. A noticeable improvement in hearing function was documented by pure tone audiometry after infusion of Rituximab. Discussion in CS, hearing function is often the most difficult parameter to control with therapy. A positive effect of Rituximab on was observed in our case. The drug also allowed to significantly reduce the number of adjuvant immunosuppressive medications.

Abstract The role of infectious agents in autoimmune diseases has been the subject of several studies and is still under investigation. Here a paediatric case series of autoimmune uveitis is reported. An exacerbation of the ocular inflammation occurred in concomitance with nasal colonisation by Staphylococcus aureus.

Background: Cogan's syndrome (CS) is a rare autoimmune vasculitis characterized by ocular inflammation and sensorineural hearing loss. CS is divided into a "typical" form with non-syphilitic interstitial keratitis and audiovestibular symptoms, and an "atypical" form with ocular involvement affecting structures other than the cornea. Anti-Hsp70 antibodies were found at variable levels in patients presenting with various forms of autoimmune sensorineural hearing loss (ASNHL)., Objectives: To assess the correlation between anti-Hsp70 antibodies and specific ASNHL subgroups., Methods: We divided 112 subjects into four groups: 14 subjects with typical CS, 24 with atypical CS, 55 with ASNHL, and 19 control subjects (healthy subjects and patients with systemic autoimmune diseases but no sensorineural hearing or audiovestibular alterations). Patients were tested for serological autoimmunity markers including anti-Hsp70., Results: Positivity of the anti-Hsp70 antibody test was highest in the typical CS group (92.9%) and lowest in the control group (5.2%). The test was positive in 52.7% of patients in the ASNHL group and 16.6% in the atypical CS group. The paired comparison analysis between groups showed that sensitivity of anti-Hsp70 in the typical CS group was significantly higher, as compared to the other three study groups., Conclusions: Anti-Hsp70 antibodies can be considered a serological marker of "typical" CS. "Atypical" CS is conceivably a sort of "melting pot" of different forms of autoimmune diseases still characterized by ocular inflammation and sensorineural hearing loss but whose antigenic characteristics need to be further defined.

Background/aims: Ocular factitious lesions involving the conjunctiva alone represent a challenging diagnosis for the ophthalmologist; corneal integrity, in fact, allows maintenance of good visual acuity and precludes the pain subsequent to trigeminal stimulation. Conjunctival biopsy is crucial to make a diagnosis and to focus on possible peculiarities in the patient's behavior. A psychiatrist has to confirm the diagnosis. In this case report, images of a bilateral pseudo-membranous conjunctivitis sparing the cornea in an anorexic adolescent boy are shown., Methods: Photographically documented case report., Results: A fourteen-year-old Italian boy was referred with a diagnosis of bilateral chronic conjunctivitis unresponsive to systemic and topical antibiotic and steroidal treatment. It had lasted for 4 months and was concomitant with an 8-kg weight loss. Conjunctival biopsy revealed cotton wool fragments. The patient admitted an unsafe behaviour lasting for months. A diagnosis of factitious conjunctivitis was made, and confirmed by a psychiatric assessment., Conclusion: Factitious lesions of the eye involve not only anatomical structures situated on the visual axis causing a reduction of visual acuity, but may also involve the conjunctiva alone. A thorough clinical history should identify the source of the patient's anxiety. Moreover, close cooperation between ophthalmologists and a psychiatrist can further clarify the diagnosis.

Purpose: This study aimed to assess the effectiveness of a steroid-sparing immunosuppressive treatment (IST) protocol in the control of severe or steroid-resistant autoimmune ocular inflammatory diseases., Methods: We carried out a prospective, non-randomized clinical study. Patients presenting with ocular inflammations that failed to respond adequately to steroids alone after monotherapy for a mean period of 9 +/- 2 months (internal control) were offered the option to switch to a combined IST. The protocol consisted of different immunosuppressive drugs added in a stepladder sequence, where each drug (including the steroids) was administered discontinuously. Main outcome measures were control of inflammation, visual acuity and safety of treatment., Results: A total of 76 subjects (121 affected eyes) enrolled in the IST protocol. Mean length of follow-up was 43 +/- 15 months. Complete control of inflammation was achieved in 86% of patients. During the first year of IST, the rate of inflammatory recurrences/patient was 0.78 +/- 1.13. This ratio diminished further during succeeding follow-up. Mean best corrected visual acuity improved from 0.31 logMAR to 0.24 logMAR (p < 0.001). Blood pressure and uric acid blood levels significantly altered for the worse in the study group., Conclusions: Immunosuppressive treatment was effective in achieving inflammatory quiescence in a large majority of patients. The study also demonstrated the longterm safety of the protocol and its steroid-sparing effect.

Background/aims: To determine the levels of cyclosporin A (CsA) in tears and the anterior segment of the eye following long-term oral intake for autoimmune diseases., Methods: Subjects taking oral CsA to treat relapsing autoimmune ocular inflammation were included in this study. All of the patients had been quiescent for at least 6 months. In patients scheduled for cataract extraction (group A), the CsA levels in the blood, aqueous humour and anterior capsule of the lens were determined. In subjects not requiring surgical intervention (group B), CsA was measured in tears and blood. The samples were analysed using turbulent flow chromatography coupled with liquid chromatography-tandem mass spectrometry (LC-MS/MS)., Results: There were 19 subjects in group A and 43 subjects in group B. CsA was detectable in all of the tear samples with a mean value of 22.4 +/- 20.2 ng/ml and there was a significant positive correlation between the CsA levels in tears and blood (P = 0.012). CsA was not detected in any of the surgical samples., Conclusion: LC-MS/MS proved very sensitive for detecting CsA in low-volume biological samples. CsA was present in human tears in proportion to the blood level after an average of 12 hours from the last oral intake.

Objectives: Autoimmune sensorineural hearing loss (ASNHL) is a relatively rare disorder which can lead to total deafness. At present, no specific laboratory test with adequate sensitivity and specificity is available to confirm the clinical suspicion of ASNHL. The aim of this study was to identify if evaluation of anti-hsp70 antibodies is an accurate diagnostic tool in patients affected by ASNHL., Study Design: Prospective study., Methods: During 4-year (2001-2005), all patients with SNHL who were referred to the Eye, Ear, Nose and Throat Department of Parma University, Italy, underwent specific tests to determine the autoimmune origin of the disease. Patients with a consistent suspicion of ASNHL underwent the routine serologic tests and a test for determination of anti-hsp70 antibodies. The same patients were divided into three groups: (1) idiopathic ASNHL; (2) ASNHL associated with ocular inflammation, i.e. Cogan's Syndrome; (3) ASNHL associated with a systemic autoimmune disease (SAD). The control group included: (1) healthy subjects; and (2) patients affected by SAD, without any ocular or audiovestibular disease., Results: 88 subjects (67 patients, defined as "study group", and 21 controls) were evaluated. Anti-hsp70 antibodies were isolated in 52% of the study group patients, and in 4% of the control group (chi2 = 13.009, p < 0.01). In the idiopathic ASNHL patients, 59.5% were found positive for anti-hsp70 antibodies. About 50% of patients affected by CS and 37.5% of patients affected by SAD with SNHL were found positive. In the control group, anti-hsp70 antibodies were found in 8.3% of healthy subjects and in none of the patients with SAD and no hearing loss., Conclusions: The present study confirms the value of the anti-hsp70 test in the serological diagnosis of autoimmune hearing loss. It is still the only available diagnostic marker that identifies an autoimmune origin of hearing loss.

Objective: The following is a case presentation of congenital syphilitic keratitis in a boy 6 years of age who was successfully treated with an immunosuppressive drug combination therapy., Methods: Congenital syphilitic keratitis was diagnosed by clinical findings and laboratory tests. The child was unresponsive to traditional treatment; thus, systemic immunosuppressive therapy, which consisted of oral cyclosporine 4 mg/kg/d, 6 days per week, and oral low-dose steroids (fluocortolone 0.8 mg/kg a week, given every other day), was initiated., Results: Corneal disease showed great improvement with this therapy, with progressive healing of lesions in the first month of treatment and no signs of toxic renal, hepatic, or growth abnormalities. Recurrences of uveitis have not occurred, and corneal interstitial keratitis episodes have been limited to 3 in an 8-year period. After 6 months with no recurrences, a tapering off of the systemic therapy was initiated, and the child is still asymptomatic and without flare-ups., Conclusions: Congenital syphilitic keratitis is usually treated with topical steroids and cycloplegic drugs, which not only can be ineffective but can also lead to complications such as cataract and glaucoma. In the present case report, a pediatric patient affected by syphilitic interstitial keratitis was treated successfully with an immunosuppressive drug combination therapy.

Purpose: To present two cases of pediatric Cogan Syndrome and to highlight the differences between the adult and pediatric forms of the disease, as well as the importance of early diagnosis and treatment., Design: Interventional case report., Methods: Institutional setting., Results: Corneal lesions were much more diffuse than those observed in adult Cogan syndrome. Immunosuppressive drug combination therapy successfully resolved systemic and ocular inflammation, but the involvement of the pupillary area caused permanent low vision in one case and amblyopia in the other., Conclusion: When chronic ocular inflammation is observed in association with sensory neural hearing loss and any systemic signs of autoimmune inflammation, a diagnosis of Cogan syndrome should be suspected. If immunosuppressive treatment is not initiated as soon as possible, permanent low vision and deafness can result.

Purpose: To test the effect of a drug combination therapy on ocular perfusion in human eyes affected by idiopathic intermediate uveitis., Methods: Seven patients (12 eyes) showing active signs of intermediate uveitis, with at least two more similar episodes reported within the previous 12 months, were enrolled in a prospective case series. Two fellow healthy eyes of two of the enrolled patients were studied as internal controls. Color Doppler imaging of the central retinal artery (CRA), the ophthalmic artery (OA), and the posterior ciliary arteries (PCAs) was performed at the time of enrollment, and at 6 and 12 months after starting treatment with oral fluorocortolone, cyclosporine, and parenteral methotrexate. The best-corrected visual acuity was concurrently measured as a second parameter., Results: In the 12 affected eyes, the mean visual acuity (+/-SD) improved from 0.15(+/-0.12) to 0.04(+/-0.18) LogMAR (paired samples Student's t-test: p = 0.015). The resistivity index (RI +/- SD) of the CRA decreased from 0.81(+/-0.13) to 0.71(+/-0.13)(p = 0.0091). Further, the variation of the RI in the PCAs reached a borderline significance (p = 0.062), decreasing from 0.71(+/-0.12) to 0.61(+/-0.12). No significant changes were observed in the OA. Moreover, eyes showing a visual improvement of > or =0.1 (LogMAR) were more likely to show a > or =10% improvement of the RI for the CRA (Fisher's exact test: p = 0.018; power = 90%; alpha probability = 5%; odds ratio = 2,4)., Conclusions: In eyes affected by idiopathic intermediate uveitis, treated with a systemic drug combination therapy, the improvement of the visual acuity seems to correlate with a proportional improvement of the retrobulbar circulation.

Purpose: To lead ophthalmologists to consider Cogan syndrome when managing a patient presenting with keratitis or other ocular inflammation accompanied by sensorineural hearing loss., Methods: Seven patients affected by Cogan syndrome were studied: two males and five females, ranging from 27 to 65 years of age (mean age: 41 years). Subjects were evaluated for a period ranging from 22 to 46 months (mean follow up time: 29.2 months). All patients were treated with immunosuppressive drug combination therapy (IDCT)., Results: Three patients were affected by classic Cogan syndrome (i.e., vestibuloauditory symptoms and later sensorineural hearing loss and interstitial keratitis). Four patients presented atypical Cogan syndrome (i.e., sensorineural hearing loss and chronic ocular inflammation such as uveitis, scleritis, conjunctivitis, retinal vasculitis, etc.). Four of these patients had a late diagnosis. Two of them were diagnosed when they already had a cochlear implant, one with bilateral deafness underwent cochlear implantation 1 year after the beginning of IDCT, one had severe bilateral hearing loss that improved during the first year of IDCT, and then rapidly worsened to total deafness in 1 month following an episode of severe systemic hypotension. Three patients who had an early diagnosis of Cogan syndrome had no worsening of vestibuloauditory dysfunction during the follow up period., Conclusion: Diagnosis of Cogan syndrome should not be overlooked by ophthalmologists in all patients with recurrent ocular inflammatory disease associated with vestibuloauditory symptoms. Early diagnosis is essential to commence the appropriate immunosuppressive therapy that may prevent permanent hearing loss and ocular dysfunction.

Objective: The aim of this study was to identify the correlation between antinuclear antibody (ANA) titre and the onset and clinical course of uveitis in children with juvenile idiopathic arthritis (JIA) or without any other systemic autoimmune disease, i.e., idiopathic uveitis (IU)., Methods: Twenty-two patients affected by uveitis were examined. Ten had JIA-associated uveitis, 12 had IU. Follow-up ranged from 7 to 101 months. The ANA were titrated three times per year and additionally in case of ocular recurrences. All patients were treated with immunosuppressive drug combination therapy (IDCT)., Results: JIA-associated uveitis: ocular recurrences were noted in three ANA-positive patients and in one ANA-negative patient. IU uveitis: ocular recurrences were noted in one ANA-positive and in one ANA-negative patient. No significant rise in ANA titre was noted in either group during uveitis recurrence., Conclusions: (1) ANA had no value in predicting the recurrence of uveitis. (2) IDCT does not influence ANA production.

The authors describe a case of hepatic hemangiomathosis in a three months old infant with a clinical picture of multiple cutaneous hemangioma, epatomegaly and severe cardiac failure. The cardiac catheterization with selective angiography showed extensive communication between the mammary artery and the hepatic circulation with the presence of large bloody areas into the markedly enlarged liver. The medical treatment with digitalis, diuretics, and corticosteroids obtained rapid resolution of the cardiac failure and of the A-V fistula signs. A clinical picture of severe liver cholostatic disease developed few months later which was confirmed by histological examination. The subsequent course has been favorable with complete clinical resolution of the liver disease.

The authors consider the problem of patency of ductus arteriosus (P.D.A.) in pre-term infants. On the basis of their own experience and reviewing international literature they discuss about mechanisms maintaining open ductus, incidence, methods of diagnosis, clinical findings and indomethacin therapy. Finally current indications for indomethacin use are discussed.

We present 11 cases of pulmonary valve stenosis who underwent percutaneous dilatation angioplasty. Patients were between 2 and 15 years old (mean age = 6.5 yrs) and all of them except 3 had moderate or severe degree of valve stenosis. Pulmonary anulus diameter ranged between 11 and 23 mm. at ECHO and between 10 and 21 mm. at angio. The catheter was chosen to be 20-40% larger than pulmonary anulus. The mean pressure gradient between RV and PA was 65 mmHg. before dilatation and 21 mmHg. after the procedure. The procedures were without complications, except one in which we observed an intermittent idioventricular rhythm for few days after the procedure. Percutaneous dilatation angioplasty has to be considered the treatment of choice for pulmonary valve stenosis.

Persistent or chronic supraventricular tachycardia is defined as the one occurring in more than 10% of cardiac rhythm during 24 hours. It may begin at any age, persisting months or years, and frequently it is discovered occasionally because it can be asymptomatic. The persistent supraventricular tachycardia (PSVT) represents 20-30% of all supraventricular tachycardias in pediatric age. The two main forms of PSVT are: atrial ectopic tachycardia, and persistent junctional reciprocating tachycardia (PJRT). The authors present 9 cases of children affected by PJRT seen from 1972 to 1985. They discuss the clinical course (mean follow up = 9.5 years), the pharmacologic treatment, the results obtained. They underline the particular resistance to conventional antiarrhythmic therapy of this form. On the other hand an antiarrhythmic treatment is recommended to avoid the risk of congestive heart failure. Nevertheless the prognosis is considered benign because in the majority of cases this type of arrhythmia disappears later on.

We have carried out an epidemiological-statistical study about congenital heart disease on 33.245 live-born infants in Parma from 1972 to 1980. 327 newborns with congenital heart disease were found; the incidence was 9,8/1000 live-born. The lowest value was 5,8/1000 live-born in 1972, the highest was 14,5/1000 live-born in 1977. In the majority of cases diagnosis was only clinical VSD, PDA, ecc.), whereas in the more complex cardiac malformations and in patients with severe congestive heart failure diagnosis was confirmed at cardiac catheterization and at surgery. In 60 cases diagnosis was confirmed also at autopsy. The congenital heart disease most frequently observed was VSD (33%), followed by PDA (13,4%) and TGA (8,8%), ecc. Clinical status at 1 year of age in all patients was evaluated. The Authors think that infant cardiac program is necessary to improve the results on congenital heart disease control.