Intravenous immunoglobulin (TVIG) therapy in pemphigus

Pemphigus is a rare, chronic, autoimmune mucocutaneous blistering disease. Treatment of pemphigus is often challenging and primarily consists of systemic corticosteroids and various immunosuppressants. When these therapies are used, we should always be careful for the side effects of long-term treatment. Intravenous immunoglobulin (IVIG) is one potential and promising therapy for patients with pemphigus, and evidence of its effectiveness and safety is increasing. A number of pemphigus patients in which IVIG treatment was beneficial have been reported. However, the mode of action of IVIG in autoimmune diseases, including pemphigus, is far from being completely understood. We here summarize the efficacy and safety profile of IVIG in pemphigus, as well as its proposed modes of action.     

Naproxen-associated linear IgA bullous dermatosis: case report and review

Linear IgA bullous dermatosis (LABD) is an acquired autoimmune subepidermal blistering disorder in which linear deposits of IgA are found along the basement membrane. Idiopathic, systemic disorder-related, and drug-induced forms of LABD have been described. Drug-induced LABD occurs in association with drug administration and resolves when the offending agent is discontinued. Other forms of LABD assume a more chronic course. The nonsteroidal anti-inflammatory drugs piroxicam and diclofenac have been previously reported to induce LABD. To our knowledge, this article describes the first documented case of LABD associated with naproxen administration, which resolved after discontinuation of the drug.     

Biological therapy of autoimmune blistering diseases

Introduction: Autoimmune blistering skin diseases are a group of disorders subdivided according to the location of blister formation: intraepidermal blistering in the pemphigus group and subepidermal in the pemphigoid group. These conditions are clinically heterogeneous and are treated with systemic corticosteroids and/or other forms of immunosuppression on the basis of clinical subtype and disease severity. These approaches may not be effective for the induction and maintenance of clinical response or need to be stopped because of intolerable side effects.

Areas covered: Biological therapies can represent a valid alternative strategy in various autoimmune blistering disorders and this review article will address this issue with a special focus on pemphigus vulgaris and bullous pemphigoid. These biological approaches are designed to target B cells, autoantibodies, complement proteins, and several cytokines.

Expert opinion: Innovative strategies for the treatment of autoimmune blistering conditions primarily depend on the use of drugs with a high degree of specificity targeting crucial steps in the immunopathology of these disorders. Novel biological agents offer treatment alternatives to patients with autoimmune blistering conditions by targeting B cells, pathogenic autoantibodies, complement and cytokines.     

Plasmapheresis therapy in pemphigus vulgaris and bullous pemphigoid.

Blistering dermatitises are characterized by the presence of blisters that begin owing to acantholysis (intraepidermic blister) such as pemphigus vulgaris (PV) or owing to dermoepidermic detachment (subepidermic blister) such as bullous pemphigoid (BP). Both diseases are autoimmune pathologies characterized by the presence of autoantibodies against specific adhesion molecules of the skin and mucous membranes. PV, in which oral lesions are always present, has a progressive course that, if the disease is not treated, nearly always brings to death from sepsis within a few years. In BP, oral lesions are rare and the disease, that is most frequent in older individuals, has a chronic course with spontaneous remissions. Systemic corticosteroids and immunosuppressants are the mainstay of treatment of these two diseases. Although this therapy had reduced the mortality of the two pathologies it is associated with serious side effects. To reduce the corticosteroids dose and to improve the symptomatology in resistant therapy cases, we treated five patients with several procedures of plasma exchange. Four patients were affected by BP and one by PV. Their disease severity at onset of plasmapheresis ranged from mild to severe. One of 5 patients suffered a plasmapheresis side effect. All patients responded with complete remission of symptomatology and had a prednisone dosage reduction until 70%. Plasmapheresis is an effective treatment for PV and BP patients who have been unresponsive to conventional therapy, for those for whom conventional drugs are contraindicated, for those who show severe clinical manifestations and for those who need high doses of corticosteroids and immunosuppressants to keep the disease under control.     

Linear IgA/IgG bullous dermatosis successfully treated with omalizumab: A case report

Linear IgA/IgG bullous dermatosis (LAGBD) is a rare, autoimmune blistering skin disease. We report a case of LAGBD in a 70‐year‐old woman. All common treatments were discontinued due to side effects or lack of treatment response. The patient was successfully treated with omalizumab which cleared her lesions after three months.     

Sequential plasmapheresis and intravenous immunoglobulin therapy for refractory myasthenia gravis: case report.

Immunotherapy is currently the standard therapy for myasthenia gravis (MG) although some patients may be refractory to treatment. We describe the use of sequential plasmapheresis and intravenous immunoglobulin (IVIG) therapy for treatment of advanced MG in a patient refractory to all forms of medical treatment including corticosteroids, immunosuppressants, and intermittent plasmapheresis. The patient, a 37-year-old woman with systemic lupus erythematosus (SLE), had initially responded well to treatment with high dose corticosteroids and intermittent plasmapheresis, with the duration of response ranging from 3 to 4 months. However, after 18 months of therapy, the duration of response had gradually decreased to 1 month. She responded well to a 5 day trial of plasmapheresis followed by high dose IVIG, and the duration of response increased to 6 months. The SLE activity was relatively silent during each relapse. This report indicates the potential usefulness of sequential plasmapheresis and IVIG in the treatment of patients with refractory MG and SLE.     

Autoimmune bullous dermatoses: a review

Bullous dermatoses can be debilitating and possibly fatal. A selection of autoimmune blistering diseases, including pemphigus vulgaris, paraneoplastic pemphigus, bullous pemphigoid, cicatricial pemphigoid, dermatitis herpetiformis and linear IgA dermatosis are reviewed. Pemphigus vulgaris usually starts in the oral mucosa followed by blistering of the skin, which is often painful. Paraneoplastic pemphigus is associated with neoplasms, most commonly of lymphoid tissue, but also Waldenstr?m's macroglobulinemia, sarcomas, thymomas and Castleman's disease. Bullous pemphigoid is characterized by large, tense bullae, but may begin as an urticarial eruption. Cicatricial (scarring) pemphigoid presents with severe, erosive lesions of the mucous membranes with skin involvement in one third of patients focused around the head and upper trunk. Dermatitis herpetiformis is intensely pruritic and chronic, characterized by papulovesicles and urticarial wheals on the extensor surfaces in a grouped or herpetiform, symmetric distribution. Linear IgA dermatosis is clinically similar to dermatitis herpetiformis, but it is not associated with gluten-sensitive enteropathy as is dermatitis herpetiformis.     

Immunotherapies in neurologic disorders

Therapy for autoimmune demyelinating disorders has evolved rapidly over the past 10 years to include traditional immunosuppressants as well as novel biologicals. Antibody-mediated neuromuscular disorders are treated with therapies that acutely modulate pathogenic antibodies or chronically inhibit the humoral immune response. In other inflammatory autoimmune disorders of the peripheral and central nervous system, corticosteroids, often combined with conventional immunosuppression, and immunomodulatory treatments are used. Because autoimmune neurologic disorders are so diverse, evidence from randomized controlled trials is limited for most of the immunotherapies used in neurology. This review provides an overview of the immunotherapies currently used for neurologic disorders.     

Necrotic Ulceration of the Hand Case Review: Think Beyond Infection

Neutrophilic dermatosis of the dorsal hands is a rare neutrophilic dermatosis that can be associated with inflammatory bowel disease, rheumatoid arthritis, and underlying malignancies. The occurrence of trauma as an initiating factor and its early features of pain and inflammation followed by blistering or ulceration mean that it can be mistaken for necrotizing infection. Neutrophilic dermatosis of the dorsal hands should be considered in all patients who present with such features confined to the back of the hands, particularly those with negative microbiological results or lack of response to antibiotic therapy. A case review design was used to analyze the presentation of a woman aged 65 years in the United Kingdom, seeking care for a painful rash on the hand in the emergency department that was subsequently diagnosed as neutrophilic dermatosis of the dorsal hands. Emergency clinician awareness of neutrophilic dermatosis of the dorsal hands as a rare differential diagnosis for patients presenting with necrotic ulceration may prevent unnecessary antibiotic therapy and surgical intervention.     

Clinical Results of Extracorporeal Photopheresis

Extracorporeal photopheresis (ECP) is a combination of leukapheresis and photodynamic therapy in which blood is treated with photoactivable drugs which are then activated with ultraviolet light and re-infused to the patient. It has been used successfully for more than 30 years in the treatment of erythrodermic cutaneous T-cell lymphoma (CTCL) and over 20 years for chronic graft-versus-host disease (GVHD). ECP has also shown promising results in the treatment of acute GVHD and other T-cell-mediated diseases, including systemic sclerosis, treatment and prevention of solid organ rejection, and more recently Crohn''s disease. The use of ECP may allow a significant reduction or even discontinuation of corticosteroids and/or other immunosuppressants, thus leading to reduced long-term morbidity and mortality and improved overall survival. ECP is a well-tolerated therapy. No significant side effects have been reported during the last 30 years. It has been shown that ECP is not associated with an increased incidence of infections, malignancies, or recurrence of underlying malignant disease, neither during short-term nor during long-term therapy.     

Topical pharmacotherapy for allergic rhinitis: new agents.

The advantages of topical (as opposed to systemic) therapy for allergic rhinitis include the avoidance of undesirable systemic effects and the concentration of therapeutic effect on the target organ. Successful topical therapy requires establishment of a proper diagnosis, followed by effective delivery of the medication to the nasal mucosa. In addition to currently available preparations such as cromolyn sodium and various corticosteroids, several other topical nasal preparations for the treatment of allergic rhinitis are under investigation. These include antihistamines (eg, levocabastine), anti-inflammatory/mast cell stabilizing drugs (eg, nedocromil), new corticosteroids (eg, triamcinolone, budesonide, fluocortin, fluticasone), anticholinergics (eg, ipratropium), and miscellaneous agents (eg, HEPP [IgE pentapeptide]).     

Changing Paradigms in ITP Management: Newer Tools for an Old Disease

Immune thrombocytopenia (ITP) is an autoimmune disease characterized by isolated thrombocytopenia that may be accompanied clinically by bleeding and reduced health-related quality of life (HRQoL). While corticosteroids, splenectomy, and various immunosuppressants (used off-label) have served as historical mainstays of ITP treatment, their use is associated with adverse effects and morbidity. Over the last 15 years, the advent of the thrombopoietin receptor agonists has revolutionized the management of chronic ITP with high response rates, durable responses, and minimal adverse effects in most patients. With four agents now FDA-approved to manage chronic ITP, there is a renewed emphasis on improving HRQoL and minimizing the toxicities associated with traditional therapies. Promising agents with diverse mechanisms of action, ranging from those targeting Bruton's Tyrosine Kinase to the neonatal Fc receptor, are currently under investigation. This review highlights recent landmark clinical trials which have made significant impacts on ITP management and ongoing drug development. In critically analyzing studies of relevance, we illustrate the changing paradigms of ITP management and how the field is advancing beyond traditional therapies.     

Treatment of pulmonary hemorrhage in childhood systemic lupus erythematosus with mycophenolate mofetil

Systemic lupus erythematosus is a chronic autoimmune disease of unknown etiology with multisystem involvement. Pulmonary hemorrhage is a major life-threatening manifestation in children and adolescents with systemic lupus erythematosus, as well as in adults. Treatment has traditionally been with high-dose corticosteroids, with or without the addition of cytotoxic agents. We report the response of a patient with childhood systemic lupus erythematosus with recurrent pulmonary hemorrhage to treatment with mycophenolate mofetil.     

免疫印迹法检测表上下大疱病患者基底膜带自身抗体

目的 探讨免疫印迹法在不同自身免疫性表皮下大疱病（ＳＡＢＤ）患者基底膜带自身抗体（ＢＭＺ抗体）分布情况及其在ＳＡＢＤ诊断和鉴别诊断中的应用价值。方法 以热分离法制备的人真皮、表皮提取物作为抗原,免疫印迹法检测９７例ＳＡＢＤ患者血清中ＢＭＺ抗体与基底膜抗原结合情况。结果 不同ＳＡＢＤ患者血清中存在结合不同真皮、表皮抗原的ＩｇＧ型和（或）ＩｇＡ型ＢＭＺ抗体。大疱性类天疱疮患者血清中ＩｇＧ和（或）ＩｇＡ     

The Changing Landscape of Alopecia Areata: An Introduction

Alopecia areata is an extremely common autoimmune condition affecting hair. Severe forms of alopecia areata exist, with existing treatments consisting of systemic immunosuppressants with numerous side effects. Recently, breakthroughs have been made in both understanding the pathogenesis of alopecia areata and the treatment thereof, which hold the promise of being able to target severe cases of alopecia areata with more efficacy and better tolerability. This article serves as an introduction to review papers from two of the leading researchers in the field of alopecia areata.     

Ocular manifestations of autoimmune disease

Rheumatoid arthritis, juvenile rheumatoid arthritis, Sj?gren's syndrome, the seronegative spondyloarthropathies, systemic lupus erythematosus, multiple sclerosis, giant cell arteritis, and Graves' disease are autoimmune disorders commonly encountered by family physicians. These autoimmune disorders can have devastating systemic and ocular effects. Ocular symptoms may include dry or red eyes, foreign-body sensation, pruritus, photophobia, pain, visual changes, and even complete loss of vision. Because a number of these diseases may initially present with ocular symptoms, physicians should maintain a high index of suspicion to make a timely diagnosis. A thorough ophthalmic examination, including visual acuity, pupillary reaction, ocular motility, confrontation field testing, external inspection, and direct ophthalmoscopy with fluorescein staining, should be completed. In the patient with the complaint of a "dry eye" or a "red eye," simple tools such as the Schirmer's test or the blanching effect of phenylephrine can be useful in diagnosis. In general, managing the systemic effects with nonsteroidal anti-inflammatory drugs, corticosteroids, and immunosuppressive agents controls the ocular symptoms. When visual function is threatened, surgical therapy may be necessary. Early and accurate diagnosis with prompt treatment or referral to an ophthalmologist may prevent systemic and ocular disabilities.     

Pemphigus vulgaris: an acquired blistering disease

Pemphigus vulgaris is one of a group of autoimmune disorders that are caused by autoantibodies against the desmoglein adhesion molecules of squamous epithelial cells. It is a rare form of immune dysfunction that can prove vexing to the patient and physician, but it has distinct clinical and histologic findings. We report a case of a patient with the autoimmune blistering disease pemphigus vulgaris localized to the oral cavity and discuss the important clinical, immunopathologic, and therapeutic factors of this disease. This case report highlights the unusual nature of pemphigus vulgaris, the modalities used in its diagnosis, and effectiveness of therapy. Pemphigus vulgaris is an uncommon disease blistering disorder due to desmoglein autoantibodies, whose presentation can be alarming and puzzling to the clinician. Awareness of the disease's presentation and mechanism will allow for an efficient diagnostic evaluation and timely treatment.     

Pruritic urticarial papules and plaques of pregnancy

Pruritic urticarial papules and plaques of pregnancy (PUPPP) is a distinct dermatosis characterized by onset in the third trimester. Lesions generally begin on the abdomen, particularly in the striae distensae. Primigravidas are disproportionately affected by this dermatosis. There is no associated fetal or maternal morbidity. Etiology and pathogenesis are unknown. The natural history is one of spontaneous resolution, and most patients respond well to symptomatic treatment with topical corticosteroids.     

Autoimmune blistering skin diseases

Emergency physicians, at the front line of patient care, are often confronted with a wide variety of dermatologic conditions. Prompt recognition is essential, especially for the autoimmune blistering skin diseases, many of which have considerable morbidity and mortality. Therefore, an accurate diagnosis is imperative for appropriate referral and initiation of therapy. This review article provides a concise yet thorough discussion of the clinical presentation, incidence, differential diagnosis and management of the commonly encountered autoimmune blistering skin diseases, some of which include pemphigus, bullous pemphigoid, and epidermolysis bullosa acquisita.     

Chronic hepatitis. The challenge of diagnosis and treatment

Chronic hepatitis can be caused by a variety of viruses or therapeutic agents, but in about 80% of cases, the cause is unknown. Distinguishing between chronic persistent and chronic active hepatitis is of primary importance in diagnosis and treatment. Percutaneous liver biopsy is necessary to make the distinction. In most cases, chronic persistent hepatitis does not necessitate specific therapy. Chronic active hepatitis responds to a wide range of therapeutic options: corticosteroids, immunosuppressants, antivirals, and immunostimulants. Prognosis depends on the risks and advantages of therapy as well as the severity and cause of the disease.