Childhood-onset myasthenia gravis with thymoma

Juvenile myasthenia gravis is an acquired, autoimmune disease occurring before age 16 years. Thymoma is exceedingly rare in children, especially in association with juvenile myasthenia gravis. We describe a 14-year-old boy with juvenile myasthenia gravis and thymoma. He presented with difficulties chewing and swallowing, nasal speech, and fluctuating weakness of the leg muscles. Neurologic examination revealed masticatory and bulbar muscle weakness with nasal speech, proximal muscle weakness, fatigability of the arms and legs, and distal muscle weakness of the legs. A diagnosis of juvenile myasthenia gravis was confirmed by a positive neostigmine test, a decremental response on repetitive nerve stimulation, and increased titers of serum anti-acetylcholine receptor antibodies. The patient received anticholinesterases, corticosteroids, azathioprine, and thymectomy. A pathohistologic analysis of the thymus gland indicated thymoma, Masaoka grade II. After 2 years of an unstable disease course, remission was achieved. Because only 10 cases of thymoma-associated myasthenia gravis are described in the pediatric population, this report offers an important contribution to a better understanding of this rare association.     

Withdrawal of antiepileptic drugs in young patients with cryptogenic focal epilepsies

PurposeThe goal of the study was to assess the outcome of antiepileptic drug (AED) withdrawal in children and adolescents with cryptogenic focal epilepsies (CFE).MethodsMedical records of consecutive patients with CFE from two referral hospitals were retrospectively evaluated over a nine-year period. Inclusion criteria were: (1) diagnosis of CFE according to the ILAE criteria, (2) less than 16 years of age at onset of epilepsy, (3) established clinical remission of at least two years before AED withdrawal, and (4) follow-up period of at least two years after withdrawal (or until seizure relapse in patients who relapsed). Time to seizure relapse and predictive factors were analyzed by survival methods.ResultsThe cohort consisted of 52 patients (16 females, 36 males). Relapse rate was 37.85%. Most relapses occurred during the first 12 months after withdrawal. Univariate analyses indicated the following factors as significantly correlated with seizure recurrences: (1) female sex; (2) age at withdrawal of AED 14 years or higher; (3) abnormal EEG before withdrawal; and (4) abnormal EEG during and after AED withdrawal. Multivariate Cox regression analyses revealed that female sex, age at withdrawal of AED 14 years or higher; and abnormal EEG during and after withdrawal were significant independent predictive factors for seizure recurrences.ConclusionThe relapse rate in our cohort was similar to the most commonly reported overall rates for childhood-onset epilepsy. Distinguishing variables—female sex, age at withdrawal greater than 14 years, and abnormal EEG – need to be considered when choosing and further following of eligible candidates for AED withdrawal.     

Angiogenesis and hypertension: the dual role of anti-hypertensive and anti-angiogenic therapies

Essential hypertension may be a consequence of structural and functional alterations of the microvascular network growth resulting partly from abnormal regulation of vascular endothelial growth factor (VEGF), one of the most potent known angiogenic factors. As data from clinical trials on anti-VEGF drugs are becoming available, it is increasingly recognized that VEGF, in addition to being a proliferation and migration factor, is also a maintenance and protection factor for endothelial cells, whose altered regulation may cause a disturbance of vascular homeostasis. Elevated VEGF levels in hypertensive patients were shown to correlate with cardiovascular risk, early microvascular and target organ damage; accordingly treatment of hypertension significantly reduced VEGF levels. Recently and in agreement with the theory that impaired angiogenesis can contribute to increased peripheral resistance and raised blood pressure (BP), an involvement of VEGF gene promoter polymorphisms in the pathophysiology of hypertension has been hypothesized. In the last decade, anti-VEGF drugs have been used in clinical practice, especially in the oncology field. This review will summarize the present understanding of the contribution of VEGF to neoangiogenesis in hypertension and its possible role as a marker of vascular damage. Given the well established effects that antihypertensive drugs exert on the vasculature beyond BP lowering (pleiotropic effects), we will also discuss the effects of antihypertensive treatment on circulating VEGF levels. The biological mechanism and clinical impact of hypertensive complications during anti-angiogenic treatments will also be reviewed.     

Concomitant drug- and infection-induced antineutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis with multispecific ANCA

OBJECTIVE: To report the first case of concomitant drug- and infection-induced antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) in a patient treated with propylthiouracil (PTU) and suffering from tuberculosis. PRESENTATION AND INTERVENTION: A 28-year-old woman with PTU-treated hyperthyroidism presented with fever, purpura, pulmonary cavitations and ANCA to myeloperoxidase, bactericidal/permeability-increasing protein (BPI), proteinase-3 and elastase. Skin histopathology confirmed vasculitis. However, sputum examination revealed Mycobacterium tuberculosis. Remission was achieved after PTU withdrawal and treatment with antituberculosis drugs. CONCLUSION: Our case confirmed that BPI-ANCA are elevated in active tuberculosis. Multispecific ANCA were helpful for the diagnosis of concomitant PTU- and M. tuberculosis-induced AAV.     

Clinical effects of topical pimecrolimus in a patient with Fox-Fordyce disease

Fox-Fordyce disease (FFD) is characterized by a pruritic eruption of skin-coloured or yellowish papules in areas rich in apocrine glands. The histology comprises dilatation of follicular infundibula with hyperkeratosis, acanthosis, and spongiosis of the infundibular epithelium with perifollicular infiltration of lymphocytes and foamy histiocytes. We treated a 12-year-old girl with FFD with topical pimecrolimus for 12 weeks, this resulted in a complete clearance of lesions. After the therapy, the patient was followed for an additional 19 months without signs of relapse. The effects of pimecrolimus in FFD might imply that an inflammatory process inducing secondary reactive hyperkeratosis could be involved in the pathogenesis of FFD.