Parkinson's disease and skin

Parkinson's disease is associated with a variety of dermatologic disorders and the study of skin may provide insights into pathophysiological mechanisms underlying this common neurodegenerative disorder. Skin disorders in patients with Parkinson's disease can be divided into two major groups: 1) non-iatrogenic disorders, including melanoma, seborrheic dermatitis, sweating disorders, bullous pemphigoid, and rosacea, and 2) iatrogenic disorders related either to systemic side effects of antiparkinsonian medications or to the delivery system of antiparkinsonian therapy, including primarily carbidopa/levodopa, rotigotine and other dopamine agonists, amantadine, catechol-O-methyl transferase inhibitors, subcutaneous apomorphine, levodopa/carbidopa intestinal gel, and deep brain stimulation. Recent advances in our understanding of the role of α-synuclein in peripheral tissues, including the skin, and research based on induced pluripotent stem cells derived from skin fibroblasts have made skin an important target for the study of Parkinson's disease pathogenesis, drug discovery, novel stem cell therapies, and diagnostics.     

Bullous,pseudobullous, & pustular dermatoses

Several dermatoses are typified by the formation of spaces (blisters; bullae) within or beneath the epidermis. These may be acellular or filled with particular species of inflammatory cells. Etiological categories include infectious, immune-mediated, genetic, drug-related, and idiopathic lesions. Examples of such disorders include impetigo, Herpes virus infections, pemphigus, bullous pemphigoid and pemphigoid gestationis, epidermolysis bullosa acquisita, IgA-related dermatoses, inherited epidermolysis bullosa variants, Hailey-Hailey disease, and porphyria cutanea tarda. Other conditions manifest microscopic acantholysis within the surface epithelium but are not associated with clinical bullae, such as Darier disease and Grover disease. Finally, both infectious and non-infectious causes exist for the development of neutrophilic pustules in the epidermis, as seen in pustular psoriasis, Sneddon-Wilkinson disease (subcorneal pustular dermatosis), and acute generalized exanthematous pustulosis. This review considers the clinical and histological features of all of these diseases.     

Skin autoimmunity and blood coagulation

Evidence exists that the immune and coagulation systems are simultaneously activated in some systemic autoimmune disorders. Although proinflammatory mediators induce tissue factor (TF) expression, the main initiator of blood coagulation, activated proteases of coagulation may act on protease-activated receptors (PAR) triggering inflammation. Such a cross-talk amplifies and maintains the activation of both systems. This review focuses on the involvement of immune and coagulation system in two skin disorders as chronic urticaria (CU), autoimmune in about 45% of cases, and bullous pemphigoid (BP), the prototype of autoimmune blistering diseases. Several investigators demonstrated the activation of coagulation in CU through the involvement of eosinophils, of TF pathway with thrombin generation and increased vascular permeability. Preliminary data indicate that anticoagulant treatment with heparin and warfarin may be effective in reducing the symptoms of this disorder. The activation of coagulation seems to display local and systemic implications in BP. Eosinophils' recruitment and thrombin generation locally contribute to the bulla formation and tissue damage. The systemic activation of coagulation may explain the increased thrombotic risk observed in these patients. Taken together, these data provide the rationale for proposing clinical trials on the anticoagulant treatment in both CU and BP patients.     

西妥昔单抗致大疱性药疹及口腔黏膜损害

1例56岁男性患者,因鼻咽癌行放疗＋西妥昔单抗分子靶向治疗。首次静脉滴注西妥昔单抗600 mg,此后400 mg/次,1次/周。首次用药后第11天患者面部及胸背部出现红色斑丘疹,并伴有脓疱,同时口腔黏膜红肿。给予氯雷他定抗过敏,呋喃西林溶液漱口。第4次用药开始将西妥昔单抗剂量减为300 mg,症状未见好转,患者出现口腔溃疡,舌体呈“地图”样改变,伴颈部皮肤糜烂。加用碳酸氢钠溶液漱口并给予抗感染等治疗。共用药6次后停用西妥昔单抗。停药后约6周患者皮肤、口腔黏膜损伤好转。     

Management of patients with ocular manifestations in vesiculobullous disorders affecting the mouth

Pemphigoid and pemphigus diseases as well as Stevens–Johnson syndrome present as vesiculobullous disorders of the skin and may additionally involve both the oral cavity and the ocular surface. Ocular involvement ranges from mild irritation and dry eye disease to chronic conjunctivitis, symblepharon, eyelid malposition, ocular surface scarring and severe visual loss. In addition to diagnostic assessments, ophthalmologists must treat the dry eye and meibomian gland dysfunction components of these diseases using a stepladder approach, including eyelid hygiene and lubricants. Topical anti‐inflammatory therapy is used to treat acute inflammatory exacerbations of the ocular surface, but it cannot prevent scarring alone. Intralesional antimetabolite therapy can cause regression of conjunctival pathology in selected cases. Hence, patients with vesiculobullous disorders should be managed by a multidisciplinary team representing ophthalmology, dermatology, otolaryngology, oral medicine and pathology, internal medicine and intensive care. Systemic treatments including corticosteroids, azathioprine, cyclophosphamide, cyclosporine and mycophenolate mofetil help control inflammation. Intravenous immunoglobulins, plasmapheresis and targeted antibody therapy can be used in selected, severe and treatment‐resistant cases. Local surgical management may include debridement of pseudomembranes, lysis of symblepharon, amniotic and mucous membrane grafting as well as reconstructive procedures. Prospective, multicentre, international studies are recommended to further support evidence‐based practice.