Therapeutic challenges in managing pediatric psoriasis.

BACKGROUND: Each year, 20,000 patients aged <10 years are diagnosed with psoriasis. Pediatric-onset psoriasis has many similarities to adult-onset disease, and previous studies suggest that the incidence might be increasing in both populations. OBJECTIVE: The challenges that arise when treating patients with psoriasis, especially those age <12 years, are summarized, as well as the limited available treatment options for treating pediatric patients with psoriasis and the evidence supporting each of them. METHODS: Recently published guidelines by the American Academy of Dermatology and the National Psoriasis Foundations, as well as guidelines published by the German Society of Dermatology, provide considerable insight in managing patients who have this condition. The latest studies on pediatric psoriasis treatment were reviewed, including recent and current clinical trials with U.S. Food and Drug Administration approved and nonapproved medications, case reports, case series, and reviews. The authors also reviewed American and European guidelines, as well as recommendations from expert panels. RESULTS: Currently, only six medications are approved by the U.S. Food and Drug Administration for the treatment of pediatric psoriasis: three biologics and three topical. Many off-label topical treatments have been used in pediatric psoriasis, with variable effectiveness and safety profiles. Data from adult clinical trials, as well as case reports and series from pediatric patients, suggest that other biologic medications are effective for pediatric psoriasis. CONCLUSION: Many questions remain unanswered, leaving clinicians facing multiple challenges when encountering pediatric patients with psoriasis. This summation will help provide an overview of current on- and off-label medications for pediatric psoriasis. Pediatric clinical trials should be implemented to obtain data that can result in expanding the therapeutic spectrum for this population, parallel to their adult counterparts.

Incidence and Risk Factors for Developing Herpes Zoster Among a Cohort of Patients Diagnosed With Lymphoma at a Community Cancer Center.

BACKGROUND: Although most cases of herpes zoster (HZ) are self-limited, lymphoma patients are at greater risk for recurrences and more serious and atypical complications that can delay scheduled anti-lymphoma treatment or prevent its continuation. PATIENTS AND METHODS: This is a cohort study with a retrospective chart review of 415 patients diagnosed with lymphoma to determine the incidence and risk factors for developing HZ among this population. Data collected included date of diagnosis, patient's age, last follow-up or death, stage and presentation of lymphoma, treatment type, baseline laboratory tests, and comorbidities. Patients with a diagnosis of HZ at any time during their course of illness were identified. Patients were divided into various subgroups to analyze their risk of developing HZ individually. The frequencies of each categorical variable were compared with χ2 tests. Relative risks were calculated using 95% confidence intervals (CIs). RESULTS: During a median follow-up of 8.9 years, 46 cases of HZ were identified, with an overall incidence density of 11.1%. Higher rates of HZ were associated with lymphocytopenia (P = .038), presentation (P = .030), stage (P = .034), autologous stem cell transplant (P = .019), multiple courses of chemotherapy (P = .035), and fludarabine therapy (P = .002). Those who received what we labeled as 'highly immunosuppressive chemotherapy' had 2.9 times the risk to develop HZ than those who did not receive this therapy (95% CI, 1.47-5.623; P < .001). CONCLUSIONS: Receiving highly immunosuppressive chemotherapy is an independent risk factor for developing HZ. Patients with the risk factors described here might benefit from antiviral prophylaxis against HZ.

Renal medullary carcinoma: a nearly fatal malignancy specifically affecting patients with a so-called benign condition.

Renal medullary carcinoma (RMC) is a highly aggressive and rare malignancy found almost exclusively in young patients with sickle cell trait (SCT). Metastatic disease is commonly present at diagnosis. There is very limited experience treating disseminated disease and the prognosis is dismal. We report the case of a young 9-year-old boy with SCT, who presented with 4 months' progression of abdominal pain, nausea and vomiting associated with cough spells, dysphagia, and weight loss. Upon evaluation, he was underweight, pale, and in mild respiratory distress. Cervical lymphadenopathy was evident and abdomen was diffusely tender. A whole-body CT scan showed a left kidney lesion with associated cervical, mediastinal, and retroperitoneal lymphadenopathy. Biopsy of a cervical lymph node revealed metastatic RMC. Patient was started on combination chemotherapy with paclitaxel, carboplatin, and gemcitabine followed by left adrenalectomy. In spite of having advanced disease, our patient achieved an excellent response with a progression-free survival of 17 months. Although SCT is thought to be a "benign" condition, RMC is one devastating complication associated with it. Considering its rarity, the near uniform associated fatality should prompt the question of whether clinical practice should change regarding proper counseling of these patients and raise awareness in the medical community.

Phosphorylation of AMPA receptors is required for sensory deprivation-induced homeostatic synaptic plasticity.

Sensory experience, and the lack thereof, can alter the function of excitatory synapses in the primary sensory cortices. Recent evidence suggests that changes in sensory experience can regulate the synaptic level of Ca(2+)-permeable AMPA receptors (CP-AMPARs). However, the molecular mechanisms underlying such a process have not been determined. We found that binocular visual deprivation, which is a well-established in vivo model to produce multiplicative synaptic scaling in visual cortex of juvenile rodents, is accompanied by an increase in the phosphorylation of AMPAR GluR1 (or GluA1) subunit at the serine 845 (S845) site and the appearance of CP-AMPARs at synapses. To address the role of GluR1-S845 in visual deprivation-induced homeostatic synaptic plasticity, we used mice lacking key phosphorylation sites on the GluR1 subunit. We found that mice specifically lacking the GluR1-S845 site (GluR1-S845A mutants), which is a substrate of cAMP-dependent kinase (PKA), show abnormal basal excitatory synaptic transmission and lack visual deprivation-induced homeostatic synaptic plasticity. We also found evidence that increasing GluR1-S845 phosphorylation alone is not sufficient to produce normal multiplicative synaptic scaling. Our study provides concrete evidence that a GluR1 dependent mechanism, especially S845 phosphorylation, is a necessary pre-requisite step for in vivo homeostatic synaptic plasticity.