Secukinumab and acitretin as a combination therapy for three clinical forms of severe psoriasis in multi‐drug refractory patients: A case series of high efficacy and safety profile

Secukinumab, the first monoclonal antibody that inhibits interleukin‐17A, has been shown to have rapid and long‐lasting efficacy in the treatment of moderate‐to‐severe psoriasis. However, there are still difficult‐to‐treat cases in which even dose‐escalation fails to provide a clinical response. In such cases, combining secukinumab with a conventional systemic agent may be a rational approach. Although methotrexate is most commonly preferred, acitretin may also be considered a good alternative, with its lower hepatotoxic potential. Data are limited regarding the use of combination therapy of secukinumab and acitretin for psoriasis. We herein present three patients with chronic plaque, generalized pustular and erythrodermic psoriasis, respectively, accompanied by multiple comorbidities, in whom skin clearance could not be achieved with several conventional and biologic therapies (including escalated dose regimens of secukinumab in two patients). Alternatively, we used a combination of secukinumab with low‐dose acitretin, which resulted in a complete or almost complete skin clearance in all patients, with no adverse events or increased toxicity. Based on our real‐life clinical experience with those patients, acitretin seems an effective and safe option to be used in combination with secukinumab. Even in patients who are refractory to multiple drugs including escalated doses of secukinumab, the addition of low‐dose acitretin may be helpful in achieving treatment goals, decreasing the need for switching to another biologic therapy.     

Cerebral vein thrombosis in Beh?et's disease.

Beh?et's disease is a chronic, relapsing multisystem disorder, and nervous system involvement is one of the serious manifestations. Neuro-Beh?et is rarely reported in children and may present with a wide variety of symptoms because the entire neuraxis may be affected. A case of cerebral vein thrombosis secondary to Beh?et's disease is presented. The patient has recovered without any visual loss and had no complaints at 1-year follow-up.     

Acute effects of gentamicin on glomerular and tubular functions in preterm neonates

It has been reported that gentamicin causes natriuresis, magnesuria and calciuria in neonates. The aim of this study was to determine the acute effects of trough and peak levels of gentamicin on the values of serum creatinine (SCr), urine albumin/urine creatinine (UA/UCr), fractional excretion of sodium and potassium (FENa, FEK) and urine calcium/urine creatinine (UCa/UCr) in preterm neonates treated with gentamicin for suspected infection. Baseline levels of serum and urine Cr, Na and K and urine albumin and Ca levels together with trough and peak gentamicin levels were measured in 61 preterm neonates at the start of the therapy, on the day of the third gentamicin dose and 48–72 h after the cessation of the gentamicin therapy. Therapeutic trough and peak levels were recorded in 56 (91.8%) and 39 (63.9%) of the preterm neonates, respectively, whereas high trough (>2 mg/dl) and peak (>9.99 mg/dl) levels were recorded in five (8.1%) and 11 (18%) of the 61 preterm neonates, respectively. Trough and peak levels of gentamicin were positively correlated with SCr, UA/UCr, FENa, FEK and UCa/UCr values. The UA/UCr, FENa and UCa/UCr values recorded during treatment were statistically significantly different from sub-therapeutic, therapeutic and high peak gentamicin levels. Gentamicin was found to have a serum peak level-dependent microalbuminuric, natriuric and calciuric effect in preterm neonates. Based on these results, we suggest that when the monitoring of serum gentamicin levels is not possible, the monitoring of UA/UCr, FENa and UCa/UCr can be useful as a noninvasive alternative.     

A case of McCune-Albright syndrome associated with Gs alpha mutation in the bone tissue

The syndrome of McCune-Albright syndrome (MAS) is clasically defined as a triad presentation with the findings of polyostotic fibrous dysplasia, café-au-lait spots, and sexual precocity. However, not all patients present with complete symptoms. A 52-year-old man was diagnosed as having a variant of McCune-Albright syndrome with the following findings: polyostotic fibrous dysplasia, acromegaly due to pituitary tumor and subclinical hyperthyroidism due to toxic multinodular goiter. Sexual precocity and café-au-lait spots were not noted. Acromegaly was confirmed by laboratory examination (IGF-1, glucose suppression test and TRH stimulation test). Long acting somatostatin analogue was used as treatment. Although the pituitary tumor could not be removed due to technical problems, mass lesions on the cranium were removed subtotally. Histopathological evaluation demonstrated that the lesion complied with fibrous dysplasia. Genomic DNAs were isolated from the craniofacial bones and peripheral leucocytes of the patient. After amplifying the related regions, Gs alpha (Gs alpha) gene was analysed by automatic DNA sequence analysis. An activating mutation of the Gs alpha gene (Arg 201 Cys) was found in the genomic DNA isolated from the bone tissue of the patient, but not in the genomic DNA isolated from the blood. We described a case of MAS associated with Gs alpha mutation in the bone tissue, presenting with polyostotic fibrous dysplasia, subclinical hyperthyroidism and acromegaly.     

Differential Diagnosis of Hereditary Nephrogenic Diabetes Insipidus with Desmopressin Infusion Test

Purpose

The causes of hereditary nephrogenic diabetes insipidus (HNDI) are the mutations in the arginine vasopressin V2 receptor gene (AVPR2) (90%) and aquaporin 2 gene (AQP2) (10%). Although it is possible to perform mutation analysis where available, differentional diagnosis at clinical bases remains valuable.

Methods

In this report we present two cases of HNDI diagnosed at clinical bases with a desmopressin infusion test as AQP2 gene mutations. The results were verified by genetic analysis to stress that a desmopressin infusion test is valuable for differential diagnosis of HNDI.

Results

With a desmopressin infusion test, factor VIII levels were increased up to 219% and 214% respectively, establishing the presence of V2 receptor. With direct sequencing of the AQP2 gene, a previously described splicing mutation in a new codon (380) and a new frameshift mutation were determined in case 1 and case 2 respectively.

Conclusion

It is concluded that the desmopressin infusion test is a simple and reliable method for the diagnosis and differential diagnosis of HNDI in early childhood.     

Reno-vascular hypertension in childhood: a nationwide survey

Renovascular disease accounts for 8–10% of all cases of paediatric hypertension, whereas, in adults, its incidence is approximately 1%. The Turkish Paediatric Hypertension Group aimed to create the first registry database for childhood renovascular hypertension in Turkey. Twenty of the 28 paediatric nephrology centres in Turkey responded to the survey and reported 45 patients (27 girls, 18 boys) with renovascular hypertension between 1990 and 2005. The age at presentation ranged from 20 days to 17 years. The mean blood pressure at the diagnosis was 169/110 mmHg. Chief complaints of symptomatic patients were headache (38%), seizure (18%), epistaxis (4%), growth retardation (4%), cognitive dysfunction (4%), polyuria (2%), palpitation (2%), and hemiplegia (2%). Renovascular hypertension was found incidentally in 11 children. The diagnosis of renovascular hypertension was established with conventional angiography in 39 patients, MR angiography in three, CT angiography in two, and captopril diethylene triamine penta-acetic acid (DTPA) scintigraphy in one patient. Twenty-one children had bilateral renal artery stenosis and 24 had unilateral renal artery stenosis. Of these, 14 (31%) had fibromuscular dysplasia; 12 (27%) Takayasu’s arteritis; six (13%) neurofibromatosis; two (5%) Williams syndrome; one (2%) Kawasaki disease; one (2%) mid-aortic syndrome; one (2%) extrinsic compression to the renal artery, and eight (18%) unspecified bilateral renal artery stenosis. Hypertension was controlled with antihypertensive drugs in 17 patients. Percutaneous transluminal angioplasty (PTRA) or surgery had to be performed in 28 patients: PTRA in 16 patients, PTRA + surgery in one patient and surgery in 11 patients (four nephrectomies). The importance of vasculitic disease, especially Takayasu’s arteritis, should not be underestimated in children with renovascular hypertension.