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Systemic Lupus Erythematosus

Neurological symptoms, including seizures and psychosis, are among the American Rheumatism Association's criteria for systemic lupus erythematosus (SLE). The presence of psychotic symptoms has been reported in about 12 of patients with SLE. Often such symptoms occur in the context of delirium (20). Serum antinuclear antibody (ANA), anti-DNA antibody, and lupus anticoagulant (LA) are serological tests commonly used to diagnosis SLE. However, there are no specific tests that correlate with the presence of psychiatric symptoms in SLE. There have been reports of a positive association between antibodies to the ribosomal p protein and the psychiatric manifestations of SLE. However, other studies have found no such association, making the use of this assay doubtful.

Neonatal Lupus Erythematosus see Fig3318

Most mothers have or will have signs of lupus erythematosus or Sjogren's syndrome. scleroderma As in lupus erythematosus, there are two forms of scleroderma that are clinically unrelated, except for some common histopathologic changes in the skin. Localized scleroderma (morphea) is a benign disease. Diffuse scleroderma (systemic sclerosis) is a serious disease.

Hsp Expression Pattern In The Lupusprone Mrllpr MOUSE

The MRL MP-lpr lpr (MRL lpr) mouse is homozygous deficient for the gene encoding the Apo-l Fas antigen and develops a lupus-like disease that is characterized by lymphoproliferation, the production of a high titer of autoantibodies to nuclear antigens, and the appearance of abnormal lymphocyte subsets (28,42). Expression of hsps in these mice showed that hsp 90 was elevated in

Associated Medical Findings

Proptosis or periorbital fullness suggests an orbital process such as Graves' disease, orbital meningioma, or orbital pseudotumor. The patient's general appearance may suggest an underlying chromosomal, endocrinological, or metabolic disorder. For instance, the disfiguring frontal bossing and enlargement of the mandible and hands are characteristic of acromegaly associated with a growth hormone-secreting pituitary adenoma. The heart rate, blood pressure, and carotid and cardiac examinations are important in any patient with a possible ischemic event. Patients with pseudotumor cerebri tend to be young females with obesity or a history of recent weight gain. Skin lesions such as erythema migrans (Lyme disease) or malar rash (systemic lupus erythematosus), and abnormal discolorations, such as cafe(c)-au-lait spots and axillary freckling (neurofibromatosis), or hypopigmented ash-leaf spots (tuberous sclerosis) also may be helpful in guiding the evaluation of patients with visual...

Acquired Thrombophilias

With circulating anti-lupus antibodies and phospholipid-dependent coagulation, while arterial thrombosis is predominantly associated with anti-cardiolipin antibodies. Most individuals with APS are otherwise healthy, but the condition occurs in patients with SLE and other autoimmune disorders, HIV infection or lymphomas. The link between antiphospholipid antibodies and thrombosis is not clear, but individuals with APS seem to have lower than normal protein S levels (e.g. Morange et al. 1997). Circulating lupus antibodies are held to suppress prostacyclin synthesis, but the evidence is not compelling. One possible mechanism entails binding of the antibodies to platelet membranes, increasing the likelihood of forming a tenase complex without the normal physiological 'priming' of the platelets. Alternatively, the antibodies might interfere with APC action at the platelet surface, or cause direct injury to the endothelial cells. Such speculations have been discussed in the literature...

Psychotic Disorders Due To General Medical Conditions That Must Be Excluded Prior To Diagnosing Schizophrenia

Psychotic symptoms can be seen in many general medical and neurological conditions (Table 1). General medical conditions in the differential diagnosis include endocrinopathies (thyroid, adrenal, pancreatic) autoimmune disorders (systemic lupus erythematosus) vascular disorders vitamin B12 deficiency and hepatic, erythropoietic, or metabolic disorders. These can generally be identified with a general chemistry screen, complete blood count, thyroid-function tests, urinalysis, and

Differential Diagnosis

Systemic lupus erythematosus See Table ,2.5.-1. Subacute lupus erythematosus See Table 25-1. Polymorphous light eruption Many cases are grossly and histologically similar to systemic or discoid lupus erythematosus but get history of presence only in summer response is faster to antimalarial drugs and locally applied sunscreening agents. Any cutaneous granulomas Such as sarcoidosis (see Chap, 20), secondary and tertiary syphilis (see Chap 16), and lupus vulgaris (see Chap 15).

Structural Abnormalities

Systemic lupus Studies of systemic disorders, such as lupus erythematosus, Sjogren's syndrome, thyroid and adrenal disease, AIDS, and cancer, describe mood symptoms in subsets of patients. As with the more diffuse neurodegenerative diseases, such as Alzheimer's disease (Cummings and Victoroff, 1990), a classic lesion-deficit approach is generally difficult because consistent focal abnormalities are uncommon. Studies of plaque loci in patients with multiple sclerosis suggest an association of depression with lesions in the temporal lobes, although it is not yet clear whether this effect is lateralized (Honer et al., 1987).

Stress Proteins in Inflammatory Liver Disease

The liver is not only involved as a bystander organ in many systemic diseases, it is also, more than most other organs, the focus of many chronic inflammatory diseases. Hepatitis B virus infection is the most prevalent infectious disease in the world, and chronic hepatitis C appears to be similarly common worldwide, although with a different geographical distribution. Alcoholic hepatitis as the inflammatory lesion in many patients with alcoholic liver disease is thought to be largely immune mediated. Although systemic autoimmune diseases like lupus erythematosus rarely affect the liver, the liver itself is the target organ of autoimmune attack in autoimmune hepatitis (which in itself is probably a heterogeneous group of diseases), primary biliary cirrhosis, amd primary sclerosing cholangitis.

The Key Role for B Lymphocytes in Autoimmune Diseases

Hormone receptor that correlate with disease severity and progression in Graves disease, and those directed to double-stranded DNA that are often elevated in lupus disease, it is becoming appreciated that B cells play more than one role in these diseases (12). Not only are they the precursors of antibody-secreting plasma cells, but they also act as remarkably effective antigen-presenting cells, suggesting that they may play a potential role in autoimmunity via abnormal autoantigen presentation. B cells can also secrete cytokines, such as TNFa, that exacerbate the autoimmune and inflammatory responses. In addition, autoreactive B cells express ligands that bind costimulatory receptors on T cells. Along with presentation of self-derived peptides on cell surface major histocompatibility complex class II molecules, this can drive activation of autoreactive T cells. Therefore, targeting B cells may prove to be an effective avenue for the development of novel therapies for systemic...

The Inhibitory Coreceptor FcyRiib A Potential Target

Previous work has demonstrated that the expression of the inhibitory Fc receptor FcyRIIB is required for the maintenance of self-tolerance (25). C57BL 6 mice deficient in this receptor develop spontaneous lupus-like autoimmunity. Several other stains of mice that develop spontaneous autoimmune disease, such as NZB, NOD, BXSB, and MLR, have also been shown to express reduced levels of FcyRIIB on activated or germinal center B cells. This reduced expression results from a polymorphism in the promoter of the corresponding gene. These results suggest that the levels of FcyRIIB expressed on some B cells may regulate their ability to maintain tolerance, and that relatively small changes in the expression of this inhibitory receptor may permit the survival and expansion of autoreactive cells (26). Thus, changes in the surface expression of this receptor appear to be critical for determining disease progression, and these changes provide a rational basis for a therapeutic approach based on...

The Role of the Complement in Autoimmune Diseases

In SLE, the first solid evidence that complement inhibitors could ameliorate target organ damage came from the finding that an inhibitory anti-C5 MAb could block the development of glomerulonephritis in the (NZB x NZW) F1 mouse model of lupus. With regard to the alternative pathway, MRL- pr mice are also protected from renal disease, as are mice in which activation of the classical and alternative pathways of C3 is partially blocked (28). Thus, it is anticipated that complement inhibitors will belong to the array of therapies available for disease management.

Interfering With Dendritic Cell Functions

A major role for dendritic cells has been established in lupus. Dendritic cell dysfunction may account for the loss of peripheral tolerance that characterizes lupus. Peripheral blood CD14+ monocytes from lupus patients, but not from normal controls, may act as mature dendritic cells that activate potentially autoreactive T cells. Maturation of these CD14+ cells is induced by elevated circulating levels of interferon-a (INFa) produced by a population of dendritic cells that infiltrate lupus lesions. These crucial pieces of evidence suggest that INFa and dendritic cells may represent therapeutic targets in patients with lupus (32,33).

Disruption of the Interferon Activating Pathway

An important clue that interferon (INF) might contribute to lupus comes from a series of studies in patients who received INFa as a therapeutic agent for viral hepatitis or carcinoid tumors. Nearly a quarter of INFa-treated subjects (22 ) developed a positive antinuclear antibodies blood test (34), and one in five (19 ) developed overt autoimmunity, including a small number who developed SLE (35). In one possible scenario, INF production promotes differentiation of SLE monocytes into activated, antigen-presenting dendritic cells, which migrate to lymph nodes and tissues, and activate autoreactive CD4+ T cells (36). T cells in turn stimulate self-reactive B cells to produce autoantibodies, particularly those with specificities for nucleic acids and associated proteins. These autoantibodies bind endogenous nucleic acids and chromatin derived from apoptotic material to form chromatin-containing immune complexes that stimulate further INF production by plasmacytoid dendritic cells (pDCs),...

Presentation and diagnosis

Routine blood counts often show a normocytic or microcytic anaemia with a neutrophil leucocytosis, although there can also be eosinophilia (especially in Churg-Strauss syndrome) and thrombocythaemia. Thrombocytopenia suggests alternative causes of lung haemorrhage such as primary haematological abnormalities or systemic lupus erythematosus, in which case there will often be accompanying low complement levels and positive antinuclear antibodies. The erythrocyte sedimentation rate and C reactive protein level will both be raised. Biochemistry will often show a low serum albumin, raised alkaline phos-phatase, and raised urea and creatinine. These results may point to a diagnosis of vasculitis but are relatively non-specific. The most important serological tests in the diagnosis of vasculitis are antineutrophil cytoplasmic antibodies (ANCA). ANCA were first described in 198226 and subsequently was found to be associated with both Wegener's granulomatosis and microscopic polyangiitis....

Immunological Abnormalities

Circulating antibodies, like lupus anticoagulant (LA) and anticardiolipin antibodies, may be related to stroke. The LA is a phospholipid antibody that interferes with the formation of the prothrombin activator. In the laboratory, there is a prolonged activated partial thromboplastin time (PTT). Some patients with LA have SLE, but most do not. When antiphospholipids of the IgG, IgM, or IgA classes are found in the absence of a known systemic illness, and patients present with an increased incidence of spontaneous abortions, thrombophlebitis, pulmonary embolism, and large- and small-artery occlusions, the disorder is now referred to as primary antiphospholipid lupus anticoagulant (APLA) syndrome. The APLA-associated stroke syndrome is characterized by its younger age at onset, predominance in women, and high risk of recurrent thrombo-occlusive events. Some patients have mitral and aortic valve vegetations and ocular ischemia. In addition to the presence of LA or anticardiolipins, or...

Gasserian Ganglion Syndromes

Trigeminal sensory neuropathy may occur in association with connective tissue disorders such as mixed connective tissues disease, systemic sclerosis, Sjogren's syndrome, and systemic lupus erythematosus. , y Symptoms including facial dysesthesias, numbness, and loss of taste may be the presenting complaints. y In such cases, based on radiographical and electrophysiological testing, involvement of the gasserian ganglion is likely. Various infectious processes within the middle cranial fossa including syphilis, tuberculosis, and bacterial meningitis can affect the gasserian ganglion by inflammation, ischemia, or direct compression. Similarly, neoplasms in this region (meningiomas, schwannomas) can compress the ganglion within Meckel's cave.

AntiCD40 Ligand Therapy

Production of pathogenic antibodies in SLE requires T-cell help along with ligation of the B-cell surface immunoglobulin receptor by antigen. It is likely that macrophages, dendritic cells, and endothelial cells are also activated by interaction with T-cells and contribute to lupus pathology. CD40 ligand (CD40L, CD154), a member of TNF family of cell surface molecules, mediates these contact-dependent signals delivered by CD4+ T helper cells to CD40+ target cells (46). indicating that such cells could account for the high-level expression of immune accessory molecules on B cells of patients with active disease. An increased serum level of soluble CD154 was also reported in SLE and RA in correlation with the relevant autoantibodies and with disease activity. Anti-CD154 antibody therapy prevents autoantibody production and renal immune complex deposition in lupus nephritis, indicating that disruption of this pathway could be a beneficial treatment in SLE (49). Clinical trials are under...

Abridged Dictionaryindex

Pustular Bacterid

Dermatologically active agents include quinacrine (Atabrine), chloroquine (Aralen), and hydroxychloroquine (Plaquenil). Their mode of action is unknown, but these agents are used in the treatment of chronic discoid lupus erythematosus and the polymorphous light eruption. Antiphospholipid antibody syndrome. Hypercoagulable state related to presence of lupus anticoagulant and anticardiolipin antibodies. Cutaneous necrosis, vasculitis, thrombophlebitis, and ecchymoses occur. Recurrent inflammatory vascular thrombosis of veins and arteries can occur throughout the body and treatment is based on anticoagulation. Recurrent fetal loss and thrombocytopenia can also occur.

Chronic Ambulatory Peritoneal Dialysis CAPD

A series of previously unreported microbes responsible for SBP have been described in CAPD. These uncommon organisms may reflect the antimicrobial inadequacies of infected intraperitonial-dialysis fluid. These organisms include (a) unspeciated, pleomorphic, nonfermenting, nonmotile, non-spore-forming gram-negative, aerobic, rod-shaped bacilli, which were isolated from the dialysate produced by the dialysis machine and from its tap water supply (b) Mycobacterium chelonei- ike organisms (c) Pseudomonas cepacia (d) Vibrio alginolyticus, which is a marine bacterium that can be recovered from fish, crustaceae, and seawater-caused peritonitis in a young man that was probably contracted during a change in peritoneal dialysis fluid after scuba diving (e) Nocardia asteroides, which was found in a patient with disseminated lupus erythematosus and chronic renal failure (f) Bacillus providence, which was recovered from a nephrectomized patient on chronic dialysis (g) Candida tropicalis...

Squamous Cell Carcinoma

As in basal cell carcinomas, many factors contribute to provide the soil for growth of a squamous cell carcinoma. A simple listing of factors is sufficient hereditarily determined type of skin age of patient (elderly) trauma from chemicals (tars, oils), heat, wind, sunlight, x-radiation, PUVA therapy (psoralen plus long wave ultraviolet light), and severe burns skin diseases that form scars, such as discoid lupus erythematosus, lupus vulgaris, and chronic ulcers ingestion of inorganic arsenic and in the natural course of xeroderma pigmentosum. Immunosuppressed patients, such as organ-transplant patients and patients with the acquired immunodeficiency syndrome, have an increased incidence of basal cell and squamous cell carcinoma. Pseudoepitheliomatous hyperplasia Primary chronic lesion, such as old stasis ulcer, bromoderma, deep mycotic infection, syphilitic gumma, lupus vulgaris, basal cell carcinoma, and pyoderma gangrenosum differentiation is often impossible clinically...

Clinical Relevance Of Hsp Overexpression

As discussed above, hsp 90 was significantly elevated in those patients with SLE who had severely active disease compared with those patients who had inactive or mildly active disease using the UCH Middlesex scoring system (12). Using a more sophisticated system, the British Isles Lupus Assessment Group's (BILAG) system for analyzing disease activity, disease activity was assessed in eight different disease categories or organ systems. Hsp levels were correlated with active or inactive disease in these eight individual disease categories in each patient at the time of sampling. Patients with SLE with active neuropsychiatric (NP) and cardiorespiratory (CR) lupus had significantly elevated hsp 90 compared with those who were inactive for disease in these categories (Fig. 1) (12). There were no differences in hsp 72 or hsp 60 levels in active compared with inactive BILAG disease categories, but hsp 73 was higher in inactive compared with active categories, and significantly so in NP and...

Diffuse Nonscarring Alopecia

One must exclude syphilis, thyroid disease, iron deficiency, drug-induced ( Ta.b e ,.27.-.4) and toxin-induced (thallium, boric acid, heavy metal) causes, and systemic lupus erythematosus and dermatomyositis as etiologic factors. When acne and hirsutism or other reasons make one suspect an androgen excess, appropriate hormonal studies should be done. Careful questioning about current or recent illness, past medical history, weight loss, recent childbirth in women, drug ingestion, hairdressing procedures, and family history of baldness is important.

Cranial Nerve Dysfunction

Oligoclonal bands (OCB) are present in the CSF when three to five bands are seen on gel electrophoresis. This finding implies that a single clonal population of plasma cells is responsible for each band. More than one oligoclonal band rarely occurs in normal CSF. A serum sample should also be obtained simultaneously with the acquisition of the CSF to determine whether the OCB are unique to the CSF. Oligoclonal bands are present in 83 to 94 percent of patients with multiple sclerosis, 100 percent of patients with subacute sclerosing panencephalitis, 25 to 50 percent of patients with other inflammatory CNS disorders (CNS lupus, neurosarcoidosis, cysticercosis, Behcet's and viral, fungal, and bacterial infections), as well as most with some brain tumors, and Guillain-Barre syndrome. Because OCBs are present in such varied conditions, their presence offers little to a specific diagnosis.

Papulosquamous Lesions

Papulosquamous Lesion

Neonatal lupus erythematosus (Fig 33-13) characterized by heart block and annular papulosquamous skin lesions on forehead and cheeks. Skin lesions usually fade by 6 to 7 months of age, while the heart block persists. This is the most common cause of neonatal heart block. Because this is maternally transmitted the mother needs to be checked for lupus. Anti-Ro or SSA antibodies may be present in mother or newborn. Figure 33-13. Neonatal lupus erythematosus.

Seborrheic dermatitis

Systemic lupus erythematosus Faint, reddish, slightly scaly, butterfly eruption, aggravated by sunlight, with fever, malaise, and positive antinuclear antibody test Chronic discoid lupus erythematosus Sharply defined, red, scaly, atrophic areas with large follicular openings with keratotic plugs, resistant to local therapy, often leaves scars (see Chap 25)

Chronic Progressive External Ophthalmoplegia and Kearns Sayre Syndrome

Conditions to exclude include other mitochondrial diseases, primarily MERRF and MELAS any disease causing ophthalmoplegia when that is the sole presenting symptom, especially myasthenia gravis other diseases that cause multisystem involvement, such as collagen vascular diseases, particularly systemic lupus erythematosus and in the appropriate setting, Lyme disease (caused by infection with Borrelia burgdorferi) or Whipple's disease. Ihe ultimate diagnosis is made by muscle biopsy and mtDNA analysis. Ihere is no proven specific treatment, although coenzyme Q10 and carnitine have been used. Implanted cardiac pacemakers can be used for conduction defects. Associated endocrine abnormalities--growth hormone deficiency, diabetes mellitus, or hypoparathyroidism--can be treated medically. Although these conditions are considered chronic, complete heart block may result in sudden death.

Combined Upper and Lower Motor Neuron Syndromes

Corticospinal tract produces an ipsilateral spastic weakness. Also, ipsilateral loss of proprioception below the level of the lesion results from interruption of the ascending fibers in the posterior columns. Loss of pain and temperature sensation occurs contralateral to the hemisection because the crossed spinothalamic tract is interrupted. The sensory level that is responsive to pain and temperature is usually located one or two segments below the level of the lesion. When the Brown-Sequard syndrome results from an extramedullary lesion, there may be segmental lower motor neuron and sensory signs at the level of the lesion due to damage to the roots and anterior horn cells, and these signs are the most reliable indication of the level of the lesion. This syndrome is most apparent in patients with traumatic hemisections of the spinal cord (e.g., due to a stab wound). Other causes are extramedullary tumors or abscesses and, less commonly, intrinsic lesions, especially vasculitis (as...

Associated Neurological Findings

The motor examination may reveal several signs relevant to the assessment of mood and thought. Any abnormality such as a hemiparesis indicates an organic disorder. The finding of myoclonus or asterixis generally indicates a metabolic or toxic disorder and occurs only rarely with focal lesions. Tremor at rest is seen with neuroleptic drug use or Parkinson's disease, and these should be considered. Rigidity and akinesia should also be assessed they may accompany catatonia, neuroleptic use, or any parkinsonian syndrome. Catatonic akinesia may include waxy flexibility and abnormal sustained postures including one limb being stretched out for extended periods. Adventitious movements such as chorea may be seen and usually indicate tardive dyskinesia following chronic exposure to dopamine-blocking drugs. Alternative explanations include dyskinesias in the presence of psychosis in Pd, Huntington's disease, Sydenham's chorea, or systemic lupus erythematosus....

Demyelinating Disorders

Autoimmune cerebritis including giant cell arterits, primary CNS artentis, and hypersensitivity arteritis and autoimmune induced dysautonomic states irom penpheral nervous system involvement including polyartentis and Wegener's granulomatosis. Systemic lupus erythematosus can affect either central or peripheral systems

Polymorphous Light Eruption

Polymorphous light eruption (PMLE) is included here, although opinion is divided as to whether it is in fact related to lupus erythematosus. PMLE is characteristically seasonal (spring or summer), implying a threshold or dose-response relationship. It most commonly affects children or young adults ( Fig.30-6).

Other types of cerebrovascular disease

One of the other causes of cerebrovascular disease is fibromuscular dysplasia, which leads to narrowed arterial segments caused by degeneration of elastic tissue, disruption and loss of the arterial muscular coat, and an increase in fibrous tissue. Inflammatory diseases of the arterial system can also lead to stroke these include meningovascular syphilis, pyogenic or tuberculous meningitis, temporal arteritis, and systemic lupus erythematosus.

Figure 2615 Periungal fibromas Koenens tumor in tuberous sclerosis

SARCOIDOSIS. (See also Chap 20.) Sarcoidosis (Fig 26-16 see Fig 20-1) is a granulomatous process affecting various organ systems. Lupus pernio, skin plaques, and maculopapular eruptions are relatively specific lesions for this disease. Lupus pernio is the most characteristic skin lesion in sarcoidosis. It consists of chronic, violaceous, indurated plaques with a predilection for the face, nose, ears and lips. Skin plaques are similar to lupus pernio, but they are located on the limbs, face, back, and buttocks. These plaques may have central atrophy or a hypopigmented appearance. Erythema nodosum is the most common nonspecific cutaneous manifestation of sarcoidosis and is a hallmark of acute disease with associated hilar adenopathy. Erythema nodosum is a hypersensitivity reaction that occurs with exposure to various antigens and appears clinically as tender, erythematous, subcutaneous nodules predominantly on the anterior shins. Other nonspecific skin changes include alopecia,...

Selected Nonatherosclerotic Occlusive Diseases

Cerebral venous thrombosis (CVT) is an uncommon condition. Basic mechanisms of CVT include venous stasis, increased clotting tendency, and traumatic or infective changes in the venous walls. Various endocrine, hematological, immunological, vasculitic, infective, and neoplastic diseases may be associated with CVT. y In neonates and children, regional infections (otitis media and mastoiditis), neonatal asphyxia, severe dehydrations, and congenital heart diseases are common associated diseases. In young women, pregnancy, puerperium, oral contraceptive pills, and various connective tissue diseases like systemic lupus erythematosus are the major causes. Other causes include malignancies, antithrombin III protein C and protein S deficiencies, and Behcalet's disease. 2 , y

Somatostatin and Somatostatin Receptors

To date, five human somatostatin receptors subtypes (sst 1-5) have been cloned (see also Chapter 2). Because they have the distinct characteristics they were divided into two classes the class I includes sst2a, sst3 and sst5 somatostatin receptors and the class II sst1 and sst4 receptors. Importantly, each of the somatostatin receptors subtype has a distinct ability of internalization . The final effect of stimulation of somatostatin receptors results from the different effects of all receptor subtypes. It is important to remember that the expression of different subtypes of somatostatin receptors in the different types of NET cancers varies even in the same type of tumor the expression can change.4 In most of tumors located in the gut the expression of sst1 and sst2 was found, and only in few of them sst5 was observed. Receptor subtype sst3 was very rarely observed in the gut carcinoids. Receptor sst4 is present in 22-86 of NET tumors. Somatostatin receptors are expressed with...


Although less common than osteonecrosis (avascular necrosis) of the femoral head, osteonecrosis of the humeral head may be caused by a number of illnesses such as alcoholism, sickle cell disease, systemic lupus erythematosus, and long-term steroid use.15 Bone scan or MRI may be used for early diagnosis, as radiographs do not show sub-chondral collapse and humeral head flattening until later in the disorder. Treatment includes rest, analgesics, physical therapy for motion, and in severe cases joint replacement.

Oral Cavity

Any discussion regarding oral cavity carcinoma should include leukoplakia which is a common finding on clinical exam. Leukoplakia is a white lesion of the oral cavity which can not be rubbed off and is not another clinical entity, such as lichen planus, candidiasis, white sponge nevus, or lupus erythematosus. In a study of leukoplastic lesions, Waldron and Shafer (1975) found 80.1 had no evidence of epithelial dysplasia. However, 12.2 showed mild to moderate epithelial dysplasia, 4.5 showed severe dysplasia or carcinoma in situ, and 3.1 showed infiltrating squamous cell carcinoma. Thus, the leukoplastic lesion runs a small but significant risk of containing or developing carcinoma. For this reason, these lesions should be biopsied and followed closely.

Skin and Mucosal DCs

In contrast with these MDC subsets, pDCs are not resident cells of normal skin and mucosa (Gilliet et al., 2004 Wollenberg et al., 2002) but are present in HPV-related cervical cancer (Bontkes et al., 2005), skin melanoma lesions (Salio et al., 2003), lupus erythematosus (Farkas et al., 2001), psoriasis (Nestle et al., 2005), allergic contact dermatitis (Bangert et al., 2003) and in the nasal mucosa as early as 6 h after allergen challenge (Jahnsen et al., 2000), suggesting an active recruitment of blood pDCs to the site of peripheral inflammation. Furthermore, pDC recruitment to the skin has been observed in a therapeutic setting in which skin tumors were treated topically with TLR7 agonist imiquimod (Urosevic et al., 2005). As will be discussed further, pDC trafficking has many similarities with T cells, both being attracted to the site of inflammation by chemokines (SDF-1 CXCR3-ligands).

Alopecia Areata

As skin disorders that can lead to a scarring hair loss one should include discoid lupus erythematosus, scleroderma, lichen planus (lichen planopilaris), fungal infections, and prolonged inflammatory tinea. Metastatic carcinoma and trauma of various types can cause scarring hair loss. A skin biopsy and a fungal culture are indicated to help establish the diagnosis in cases of scarring alopecia ( Fig 27.16).

Concluding Remarks

With the progression of our knowledge on DC biology, it appears that DCs are central to the immune system. They are among the first cells to encounter a pathogen, together with epithelial cells, and their intrinsic properties as well as mode of activation have a great impact on the subsequent adaptive immune response. This central role is illustrated by the increasing number of disease situations where MDC function was found to be abnormally increased, such as allergy (Holt and Stumbles, 2000 Lambrecht et al., 2001 Soumelis and Liu, 2004) and autoimmunity (Pulendran et al., 2001c), or decreased, such as neoplasia (Banchereau and Palucka, 2005) or various immune deficiencies, including, but not restricted to, HIV. Although more recently described, pDCs have also been implicated in various pathologic conditions. pDC activation to produce type I IFNs could be a major factor in the pathophysiology of autoimmune diseases such as lupus erythematosus (Blanco et al., 2001 Lovgren et al., 2004...


Amphetamine use has also been associated with movement disorders. The presence of continuous buccal-oral movements was noted to be a characteristic sign of amphetamine abusers and thought to be helpful in diagnosis (195). In a study of the influence of amphetamine on chorea (196), patients with Huntington's chorea, patients with Sydenham's chorea, and one patient with lupus erythematosus (with right hemichorea), in addition to normal volunteers, were each given one 10-mg dose of D-amphetamine intravenously. The amphetamine worsened the chorea of the Huntington's and Sydenham's patients, but caused no movement disorders in the control group or in the

Acquired atrophies

From inflammatory diseases such as syphilis, chronic discoid lupus erythematosus, leprosy, tuberculosis, scleroderma, etc. Autoeczematization. See Id reaction Chilblain lupus erythematosus of Hutchinson. Subtype of lupus erythematosus with cold induced, red, ulcerative symmetrical lesions on ears, nose, digits, knees and elbows.

DHEA therapy

Other proposed uses for DHEA therapy In addition to theoretical anti-aging effects and potentially beneficial metabolic effects of DHEA supplementation, the effects of exogenous DHEA administration have been studied in other conditions. Beneficial effects on mood have been observed while using DHEA as treatment for depression and dysthymia 314,315 . DHEA supplementation in Alzheimer disease has been shown to cause only minor and transient improvements in cognitive performance 316 . In terms of bone health, the beneficial effects of DHEA supplementation are felt to be minor and limited to women 314 . DHEA supplementation has been shown to reduce the frequency of flares, and to decrease steroid dose requirements, in women with systemic lupus erythematosus 314,316 . DHEA has also been studied as a potential chemopreventive, anticarcinogenic agent 317 . The potential for immunoregulatory effects of DHEA has been demonstrated by the presence of specific binding found in murine T cells 318...


Sys-temic lupus erythematosus (Fig 26 17A B see Fig,. 25-1, Fig 25-2, Fig.,25-3, Fig 25-4 and Fig 34-1.1) is a occasion, the atrophic, hyperpigmented, scarring lesions of chronic cutaneous lupus erythematosus (discoid lupus erythematosus) (see Fig 25.-1 and Fig 25-3) may develop, while the annular or papulosquamous lesions of subacute cutaneous lupus erythematosus (see Fig 25.-2. and Fig 2.6. .1.7.B ) have a more frequent association with systemic disease. Panniculitis (lupus profundus), vasculitis, alopecia, livedo reticularis, and periungual telangiectasias are some of the other skin findings that can be seen in systemic lupus erythematosus. Wechsler HL. Cutaneous disease in systemic lupus erythematosus. Clin Dermatol 1985 3 79.

Clinical Features

The differential diagnosis of hypochondriasis is important to keep in mind when evaluating the patient. First, a medical condition must be excluded. Given that some medical diseases may be hard to exclude completely because their early stages are less apparent or because adequate laboratory diagnostic tools are unavailable for them (e.g., multiple sclerosis, systemic lupus erythematosus, Lyme disease, occult malignancies), the physician working with a patient whose hypochondriasis does not improve with psychiatric treatment should reconsider the possibility that a diagnosis of medical illness has been missed. Similar to somatization disorder, hypochondriasis is characterized by the presence of unexplained symptoms or sensations. However, the patient with hypochondriasis takes these symptoms one step further by leaping to a catastrophic cognitive misinterpretation of the significance of these symptoms.

Atopic eczema

This case of facial atopic eczema (top) resembled acute lupus erythematosus. The arm eruption (bottom) is on another patient and exemplifies the chronic lichenified form of atopic eczema. (K.U.M.C. Dome Chemicals) Figure 9-13. Drug eruptions. (A) Erosions of tongue and lips from sulfonamides. (B) Bismuth line of gums. (C) Phenolphthalein fixed eruption of lips of an African-American boy. (D) Whitening of scalp hair from chloroquine therapy for lupus erythematosus. ( E) Erythema multiforme-like eruption of palm from oral antibiotic therapy. (F) Striae of buttocks of 30-year-old man following 9 months of corticosteroid therapy. ( G) Papulosquamous eruption of chest from phenolphthalein. (E.R. APRESOLINE. Systemic lupus erythematosus-like reaction occurs. MINOCYCLINE. This can discolor skin (muddy skin syndrome), teeth, and scars. Rarely hypersensitivity, sickness-like reaction and drug-induced lupus erythematosus. Rare syndrome of hepatitis, exfoliative...

Mediastinal Tumors

Most mediastinal tumors do not have known risk factors. Patients with Von Recklinghausen's disease have a high incidence of neurogenic tumors. For the most part, these tumors are neurofibromas of the posterior compartment. Tumors of the thymus gland have many associated syndromes, the most common of which is myasthenia gravis. Myasthenia gravis is present in 30-50 of patients with thymoma. Of all patients with myasthenia gravis, only 15 have a thymoma. Other conditions associated with thymoma include pure red cell aplasia, hypogam-maglobulinemia, myotonic dystrophy, and systemic lupus.


On the other hand, photoaging (genesis of solar elastosis) is attributed to chronic UVA radiation. Additionally, UVA is the major waveband responsible for polymorphic light eruption, the most common form of the idiopathic photodermatoses. The immediate darkening of the skin is an acute effect related to UVA, but a certain carcinogenic potential of UVA is also discussed 4 . Furthermore, UVB and especially UVA2 (290-320 and 320-340 nm) have been associated with the exacerbation of autoimmune dermatosis, e.g. subacute cutaneous lupus erythematosus 5 . Solar-stimulated UV radiation, particularly UVA2 (320-340 nm) applied after immunization in mice has been shown to suppress immunological memory and the elicitation of delayed-type hypersensitivity 6 .


The superficial lesions consist of reddish papules, nodules, and plaques, which may be multiple or solitary and of varying size and configuration. Annular forms of skin sarcoidosis are common. These superficial lesions usually involve the face, the shoulders, and the arms. Infiltration of sarcoidal lesions frequently occurs at scar sites. Subcutaneous nodular forms and telangiectatic, ulcerative, erythrodermic, and ichthyosiform types are rare. Lupus pernio is most often seen in African-American females. It is often associated with chronic systemic disease. Erythema nodosum is characteristic of acute benign sarcoidosis (see Chap.12). Lupus pernio (indurated violaceous lesions on ears, nose, lips, cheeks, and forehead) and plaques are characteristic of chronic, severe, systemic disease.

Fordyces disease

Thrombocytopenia, pernicious anemia, cyclic or periodic neutropenia), immunocompromised conditions (such as the acquired immuno-deficiency syndrome, organ transplants, lymphomas), collagen diseases (lupus erythematosus and scleroderma), pigmentary diseases (e.g., Addison's disease, Peutz-Jeghers syndrome), and autoimmune diseases, which cross over in several categories but include pemphigus and pemphigoid, and possibly benign mucosal pemphigoid.


Systemic Lupus Erythematosus Patients with the more severe manifestations of this disease may develop one or more cytopenias, particularly thrombocytopenia. Usually, these cytopenias are manageable by effective treatment of the underlying disease. In a few patients, the cytopenia is severe and is refractory to nonoperative measures. Splenectomy brings about a prompt cytologic improvement in approximately two thirds of patients, but late relapse is more common than in patients with ITP or AIHA. The more severe the lupus, the greater the chance of a less than optimal response or of a late relapse. No laboratory measures are of value in predicting who will respond to splenectomy.

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