Challenges in the diagnosis and treatment of disabling pansclerotic morphea of childhood: case-based review.

Disabling pansclerotic morphea of childhood (DPMC) is a rare subtype of juvenile localized scleroderma (JLS) characterized by pansclerosis mainly affecting children under the age of 14. This aggressive disease has a poor prognosis due to the rapid progression of deep musculoskeletal atrophy resulting in cutaneous ulceration and severe joint contractures. We describe the challenges in treating a previously well 5-year-old male who has refractory symptoms of DPMC. Over the 29 months, since his initial presentation, we trialed over ten therapies. There was subjective improvement with prednisolone and mycophenolate mofetil (MMF). However, other therapies including biologics and tyrosine kinase inhibitors (TKI) were ineffective. The patient has been referred for hematopoietic stem cell transplant given ongoing disease progression. We conducted a literature search focusing on English articles with keywords including DPMC. Publications with limited information or describing cases aged 20 and above were excluded. Thirty-seven case reports were identified and the reported treatments were evaluated. Methotrexate and corticosteroids have been the most commonly utilized. MMF has been anecdotally effective. Biologics, TKI, and Janus kinase inhibitors lack evidence in DPMC, but have had demonstrated efficacy in similar pathologies including systemic sclerosis, and, thus, have been used for DPMC. Phototherapy has been documented to be reducing skin thickness and stiffness of plaques. Eventually, most children require multi-modal and high-dose immunosuppressive therapies to reduce the inflammation inflicted by the disease. Long-term antibiotics and nutritional support are important in the ongoing care of these patients.

Special biological issues in the management of women with schizophrenia.

Schizophrenia is a debilitating and pervasive mental illness with devastating effects on psychological, cognitive and social wellbeing, and for which current treatment options are far from ideal. Gender differences and the influence of the female reproductive life cycle on the onset, course and symptoms of schizophrenia and the discovery of estrogen's remarkable psychoprotective properties in animal models led to the proposal of the 'estrogen protection hypothesis' of schizophrenia. This has fueled the recent successful investigation of estradiol as a potential adjuvant therapeutic agent in the management of schizophrenia in women. This review explains the scientific rationale behind the estrogen hypothesis and how it can be clinically utilized to address concerns unique to the care of women with schizophrenia.