Antiphospholipid syndrome in a patient with rheumatoid arthritis.

Antiphospholipid syndrome (APS) is an autoimmune condition characterized by a thrombotic event and/or pregnancy morbidity in the presence of persistently elevated antiphospholipid (aPL) antibody titers, which are most prevalent in patients with systemic lupus erythematosus but also have been associated with other autoimmune, malignant, and infectious diseases. In contrast to the clear correlation between high aPL antibody titers and thrombotic events in patients with systemic lupus erythematosus, the pathogenic role of these autoantibodies in association with other diseases, such as rheumatoid arthritis (RA), is not as well defined. We report a case of APS manifesting as cutaneous ulceration and necrosis in a patient with severe RA.

Granulomatous dysimmune reactions (sarcoidosis, granuloma annulare, and others) on differently injured skin areas.

Granulomatous disorders are chronic cell-mediated immune responses histologically characterized by collections of macrophages, epithelioid cells, and multinucleated giant cells. This disease spectrum often has an infectious origin, but sometimes neither an infective agent nor an inciting antigenic stimulus can be identified. The skin may be a preferential target for these disorders, especially in the areas that have been damaged by various forms of skin injury (eg, herpetic infections, trauma, thermal or solar burns, vaccinations, tattoos). These damaged skin sites frame the new concept of an immunocompromised cutaneous district (ICD), which defines a skin area with acquired immune dysregulation that can pave the way for the local onset of opportunistic disorders, such as infections, tumors, and granulomatous disorders. Sarcoidosis, granuloma annulare (GA), and forms of granulomatous vasculitis, such as Churg-Strauss syndrome (CSS) and Wegener's granulomatosis (WG), are the most common granulomatous disorders that occur in an ICD and may share common pathogenic mechanisms. Recent studies have found clinical and pathologic overlapping features across noninfectious granulomas. Although no unifying etiology exists, the development of granulomatous processes in the ICD has often been reported and the literature contains various hypotheses to explain it: (1) overactive immune response in a previously injured region with or without loss of immune tolerance; (2) overall reduced immune response; (3) retention of an exogeneous antigen or foreign body; (4) altered neural signaling; and (5) a combination of all the aforementioned processes. T helper cells, T regulatory cells, and macrophages, as well as a number of antigenic proteins, have been identified as potential contributing factors. In addition, a genetic predisposition and an intact systemic immune system are both instrumental for the persistence of local granuloma formation in the ICD.

Update on tanning: More risks, fewer benefits.

The tanning response, classically defined as increased cutaneous pigmentation after solar ultraviolet light exposure, encompasses a variety of protective, reparative, and cosmetic issues. The tanning story is continuously evolving as basic science, clinical research, and public health studies shed light on topics involving: the physiologic mechanisms of tanning, the medical benefits of tanning, the role of sunscreens, the development of "sunless" self-tanners, the use of photocarcinogenic indoor tanning services, and the relatively recent development and promulgation of α-melanocyte-stimulating hormone analogues. High-risk tanning behaviors have become increasingly popular and the incidence of melanoma has risen more rapidly than any other cancer. This review will focus on the risks and benefits of each type of tanning, with an emphasis on issues pertinent to dermatologists who care for adolescents and young adults.

De novo microdeletion of Xp11.3 exclusively encompassing the monoamine oxidase A and B genes in a male infant with episodic hypotonia: a genomics approach to personalized medicine.

Monoamine oxidase A and B (MAOA and MAOB) play key roles in deaminating neurotransmitters and various other biogenic amines. Patients deficient in one or both enzymes have distinct metabolic and neurologic profiles. MAOB deficient patients exhibit normal clinical characteristics and behavior, while MAOA deficient patients have borderline intellectual deficiency and impaired impulse control. Patients who lack both MAOA and MAOB have the most extreme laboratory values (urine, blood, and CSF serotonin 4-6 times normal, with elevated O-methylated amine metabolites and reduced deaminated metabolites) in addition to severe intellectual deficiency and behavioral problems. Mice lacking maoa and moab exhibit decreased proliferation of neural stem cells beginning in late gestation and persisting into adulthood. These mice show significantly increased monoamine levels, particularly serotonin, as well as anxiety-like behaviors as adults, suggesting that brain maturation in late embryonic development is adversely affected by elevated serotonin levels. We report the case of a male infant with a de novo Xp11.3 microdeletion exclusively encompassing the MAOA and MAOB genes. This newly recognized X-linked disorder is characterized by severe intellectual disability and unusual episodes of hypotonia, which resemble atonic seizures, but have no EEG correlate. A customized low dietary amine diet was implemented in an attempt to prevent the cardiovascular complications that can result from the excessive intake of these compounds. This is the second report of this deletion and the first attempt to maintain the patient's cardiovascular health through dietary manipulation. Even though a diet low in tyramine, phenylethylamine, and dopa/dopamine is necessary for long-term management, it will not rescue the abnormal monoamine profile seen in combined MAOA and MAOB deficiency. Our patient displays markedly elevated levels of serotonin in blood, serum, urine, and CSF while on this diet. Serotonin biosynthesis inhibitors like para-chlorophenylalanine and p-ethynylphenylalanine may be needed to lower serotonin levels in patients with absent monoamine oxidase enzymes.