Morgellons disease and delusions of parasitosis.

Morgellons disease is a controversial and poorly defined symptom cluster of skin lesions and somatic symptoms, most notably 'fibers' in the skin. Because of widespread coverage in the media and on the Internet, there are an increasing number of patients presenting to dermatologists. We present three patients who believed that they had fibers in their skin. We offer a discussion of delusions of parasitosis to demonstrate similarities between these conditions. It has been suggested by a limited number of healthcare providers that an unknown infectious agent underlies this symptom complex yet no available evidence supports this assertion. Laboratory values that would be reflective of an infectious process (e.g. elevated white blood cells, sedimentation rate, C reactive protein) are routinely normal and biopsies often reflect only nonspecific findings such as acute and chronic inflammation with erosion or ulceration. Patients with Morgellons disease generally lack insight into their disease and reject the need for psychiatric help. The goal is to build trust and refrain from minimizing what the patient experiences. Attentive examination of the patient's skin and fragments they present is necessary to rule out a true underlying pathologic process and to establish a trusting relationship. A supportive, non-confrontational approach is ideal. The patient is best treated by a team of practitioners of several specialties, including dermatologists, psychiatrists, and counselors.

Kaposi varicelliform eruption (eczema herpeticum).

A 35-year-old woman with a history of atopic diathesis presented to the emergency department with 2 weeks of widespread facial vesiculopustules and eroded vesicles. HSV-1 was found on viral culture and direct fluorescent antibody testing. She was diagnosed with eczema herpeticum, an uncommon and potentially life-threatening viral infection that arises in areas of pre-existing dermatosis. Antiviral treatment for eczema herpeticum is very effective, and should be instituted without delay to avoid significant morbidity and mortality.

Delusional disorders in dermatology: a brief review.

There are several unique psychiatric disorders that are likely to present to a dermatologist because of their accompanying skin complaints. Delusions of parasitosis (DP) is a fixed, false belief of parasitic infestation that may lead patients to compulsively self-mutilate while attempting to remove the non-existent parasites. Morgellons disease is a controversial condition characterized by a fixed belief that fibers that are imbedded or extruding from the skin; this condition is likely in the spectrum of DP. Body dysmorphic disorder (BDD) is a preoccupation with an imagined defect in appearance that causes significant distress and is associated with time consuming rituals, isolation, depression, and increased risk of suicide. Olfactory reference syndrome (ORS) is a preoccupation with body odor leading to the stigmata of shame, embarrassment, and social isolation. This brief review examines each of these conditions and their management because any one of them may present to a dermatologist.

Severe drug hypersensitivity reaction in a young woman treated with doxycycline.

Doxycycline is a commonly prescribed medication for the management of acne vulgaris. Severe adverse reactions to this medication are uncommon. We describe an unusual case of a 20-year-old female who experienced a life-threatening hypersensitivity reaction, including fever, lymphadenopathy, hepatitis, nephritis and severe pneumonitis with respiratory failure following oral administration of doxycycline for facial acne.

Abnormal wound healing: keloids.

Wound healing is a complex and carefully regulated physiologic response to a traumatic injury. Deregulation of this coordinated process can lead to exuberant scar formation as seen in keloids and hypertrophic scars. Despite their common occurrence, keloids remain one of the most challenging dermatologic conditions to successfully treat and may have significant psychosocial impact for the patient. In this review, we discuss the clinical features, genetics, epidemiology, and treatment of keloids.

Keloids: pathophysiology and management.

Keloid formation occurs as a result of abnormal wound healing. Despite the high prevalence of keloids in the general population, they remain one of the more challenging dermatologic conditions to manage. More than a cosmetic nuisance, they are often symptomatic and can have a significant psychosocial burden for the patient. Although multiple treatment modalities exist, no single treatment has proven widely effective. In fact, recurrence following treatment is generally the norm. Combination therapy is likely the optimal strategy. In this review, we highlight the clinical features, pathophysiology and management of keloids.

West Nile virus infection in the pediatric population.

In 2004, Los Angeles County confirmed 11 cases of symptomatic West Nile virus (WNV) infections in children younger than 18 years of age. Eight had WNV fever, 2 had meningitis and 1 had encephalitis. Fever, rash, nausea and vomiting were the most prominent symptoms at presentation; median duration of illness was 7 days. Clinicians should be aware of the risk of WNV illness, confirm this diagnosis and report suspected WNV cases to their local health department.

Neonatal lupus.

An otherwise healthy 5-week-old infant with erythematous plaques predominantly on the face and scalp presented to our dermatology clinic. The mother had been diagnosed with lupus erythematosus 2 years earlier but her disease was quiescent. Neonatal lupus is a rare condition associated with transplacental transfer of IgG anti-SSA/Ro and anti-SSB/La antibodies from the mother to the fetus. Active connective tissue disease in the mother does not have to be present and in fact is often absent. Although the cutaneous, hematologic and hepatic manifestations are transient, the potential for permanent heart block makes it necessary for this to be carefully ruled out. As in this case, the dermatologist may be the one to make the diagnosis and should be aware of the clinical presentation, work-up, and management of this important disease.

Homozygosity for premature stop codon of the MHC class I chain-related gene A (MIC-A) is associated with early activation of islet autoimmunity of DR3/4-DQ2/8 high risk DAISY relatives.

We hypothesized that homozygosity for the major histocompatibility complex (MHC) class I chain-related gene A (MIC-A)5.1 allele with premature stop codon would increase diabetes risk of individuals followed from infancy in the DAISY study (Diabetes Autoimmunity Study in the young). Forty five percent (10/22) of relatives (siblings and offspring cohort, SOC) who developed anti-islet autoantibodies were MIC-A5.1/5.1 homozygous. Of SOC individuals without autoantibodies, 12/58 (19%, p = 0.02) were MIC-A5.1 homozygous. By life table analysis of expression of autoantibodies, DR3-DQ2/ DR4-DQ8 more than 50% of MIC-A5.1 homozygous children became autoantibody positive by 7 years of age, compared to delayed development of autoantibodies for non-MIC-A5.1/5.1 DR3-DQ2/ DR4-DQ8 children (p = 0.005). For DR3-DQ2/DR4-DQ8 nonrelatives, the risk of activating anti-islet autoimmunity remained low even with MIC-A5.1 homozygosity suggesting that there are additional factors contributing to the marked risk of relatives compared to the general population with the DR3-DQ2/DR4-DQ8 genotype.

"Extended" A1, B8, DR3 haplotype shows remarkable linkage disequilibrium but is similar to nonextended haplotypes in terms of diabetes risk.

To evaluate potential differential diabetes risk of DR3 haplotypes we have evaluated class I alleles as well as two microsatellites previously associated with differential risk associated with DR3 haplotypes. We found that over one-third of patient DR3 chromosomes consisted of an extended DR3 haplotype, from DQ2 to D6S2223 (DQ2, DR3, D6S273-143, MIC-A5.1, HLA-B8, HLA-Cw7, HLA-A1, and D6S2223-177) with an identical extended haplotype in controls. The extended haplotype was present more frequently (35.1% of autoimmune-associated DR3 haplotypes, 39.4% of control DR3 haplotypes) than other haplotypes (no other haplotype >5% of DR3 haplotypes) and remarkably conserved, but it was not transmitted from parents to affected children more frequently than nonconserved DR3-bearing haplotypes. This suggests that if all alleles are truly identical for the major A1, B8, DR3 haplotype (between A1 and DR3), with different alleles on nonconserved haplotypes without differential diabetes risk, then in this region of the genome DR3-DQ2 may be the primary polymorphisms of common haplotypes contributing to diabetes risk.

Insulin autoantibodies are associated with islet inflammation but not always related to diabetes progression in NOD congenic mice.

Susceptibility to diabetes in humans and nonobese diabetic (NOD) mice is believed to arise from the combined effect of multiple genetic loci, resulting in immune-mediated destruction of the insulin-secreting beta-cells. Insulin autoantibodies (IAAs) are often present in humans for years, and in NOD mice for weeks, before the onset of diabetes. We have evaluated the expression of IAAs in NOD mice and in diabetes-resistant NOD congenic strains to characterize the association of autoantibody expression with insulitis and diabetes. In NOD congenic strains with genes that contribute to protection from insulitis and diabetes (Idd3, Idd5, Idd10, and Idd18), the prevalence of IAAs is reduced relative to NOD mice. In contrast, NOD.B10 Idd9 mice have a high prevalence of IAAs and a high degree of insulitis, despite a nearly complete resistance to diabetes. These data indicate that IAA expression is a phenotype that is associated with insulitis and correlates with overall disease progression in some strains of congenic mice but not in others. It is likely that patients with type 1 diabetes will also show non-major histocompatibility complex genetically determined variation in expression of autoantibodies and progression to diabetes.

Immunology primer.

The immune system, through a complex interplay of highly specialized cells and a seemingly endless number of soluble mediators, works to ensure protection from the potentially harmful pathogens that we encounter in our lifetime. The development of the immune system is a compromise between the necessity to recognize foreign peptides in the context of self-molecules (MHC) and the need to be tolerant to all self-peptides. Despite the large number of mechanisms in place to ensure the removal or suppression of self-reactive lymphocytes, the system is not 100% effective, with the occasional result of autoimmunity. A number of autoimmune disorders occur together and a better understanding of the genetic basis underlying this association should lead to an enhanced ability to predict, diagnose, and develop therapies aimed at preventing and treating these diseases.

The genetics of autoimmune polyendocrine syndrome type II.

A series of autoimmune disorders, often Addison's disease, type 1 diabetes mellitus, and thyroid autoimmunity, frequently occurs together in patients with the autoimmune polyendocrine syndrome type II (APS-II). The highest risk HLA genotype for Addison's disease, either as a single disease or in APS-II patients, consists of the genotype DR3/4, DQ2/DQ8 with DRB1*0404. As many as 30% of patients with Addison's disease have this genotype versus less than 0.5% of controls. An additional and important associated locus within the HLA region is the class I related gene, MIC-A. Patients who develop Addison's disease often have a delayed diagnosis and may die from Addisonian crisis; therefore, improved genetic testing combined with testing for 21-hydroxylase autoantibodies might allow the identification of relatively high-risk populations (greater than 1 in 200 defined genetic risk compared with 1 in 10,000 population risk).

Millennium award recipient contribution. Identification of children with early onset and high incidence of anti-islet autoantibodies.

A total of 21,000 general population newborns (NECs) and 693 young siblings-offspring of patients with type 1A diabetes (SOCs) were class II genotyped and 293 NECs and 72 SOCs with the high-risk genotype, DR3/4, DQB1*0302 have been prospectively evaluated. Seventeen individuals who converted to persistent autoantibody positivity and two autoantibody-negative control groups (35 SOCs and 24 NECs) were typed for HLA-A class I alleles. The A1, A2 genotype was significantly increased among the autoantibody-positive subjects (47%) compared to autoantibody-negative SOCs (14%, P = 0.01) and NECs (13%, P = 0.02). Life-table analysis of DR3/4, DQB1*0302 siblings revealed a risk of 75% for development of islet autoantibodies by the age of 2 years for those with A1, A2. The HLA-A2 phenotype frequency was increased among an independent DR3/4, DQB1*0302 young diabetes cohort (64% versus 33% for autoantibody-negative NECs). These results suggest that a high incidence and early appearance of islet autoantibodies for siblings of patients with type 1A diabetes are associated with DR3/4, DQB1*0302 and potentially increased with HLA-A genotype A1, A2.

Insulin autoimmunity: prediction/precipitation/prevention type 1A diabetes.

Type 1 diabetes of both the NOD mouse and man is associated with autoimmunity directed against insulin which is the only beta cell specific autoantigen identified to date. One can use autoantibodies to insulin to predict diabetes, use insulin peptides to create insulin autoantibodies, insulitis and diabetes, and use insulin or its peptides in animal models to prevent diabetes. An expanding set of resources are now available for the development and testing in man of therapies to prevent type 1 diabetes, and a number of trials utilizing insulin peptides are now underway.