Inheritance Of Psoriasis Research Articles

Gender-related differences in patients with psoriatic arthritis

Psoriatic arthritis (PsA) is an inflammatory arthritis that affects up to 30% of patients with psoriasis. Gender-related differences have been extensively investigated in spondyloarthritis, particularly in ankylosing spondylitis, which shares several genetic and clinical characteristics with PsA. PsA affects men and women equally. Sex may play a role in the underlying genetic mechanisms of PsA. The inheritance of psoriasis and PsA may be implicated by genomic imprinting, which is a differential expression of a gene depending on the sex of the transmitting parent. Gender-related differences are observed in the clinical expression of PsA. Males are more likely to develop axial involvement, while women tend to present with peripheral polyarticular disease. Men also develop more severe radiographic damage in their spine, as well as in their peripheral joints. Women tend to discontinue treatment with anti-TNF-α agents earlier than men owing to inferior response and more side effects. Women with PsA also tend t...

Psoriasis.

Psoriasis is a common inherited skin disorder. Approximately 2% of the United States population is affected, with 25% to 45% of individuals developing their first clinical signs before 16 years of age. Thus, it is of great importance for all pediatric clinicians to be familiar with this papulosquamous skin disorder.Classic lesions of psoriasis consist of round, erythematous, well-marginated plaques covered by a grayish or silvery white scale. The scale is generally attached at the center rather than at the periphery, and its removal results in fine punctate bleeding. This is called the Auspitz sign and is highly characteristic but not diagnostic of psoriasis. Common sites of involvement are the scalp, elbows, knees, and gluteal crease, resulting in “gluteal pinking.” The amount of body surface area involved varies from trivial to widespread. Nail pitting, when present, is a helpful diagnostic clue. Although psoriasis usually is considered a pruritic disorder, itching can be quite variable. Involvement of the diaper area is quite common in infants and toddlers. Initially,lesions often look like candidal diaper dermatitis with a bright red rash involving the creases. In psoriasis, the rash can spread to the abdomen and legs. The clinician should include psoriasis in the differential diagnosis of any extensive or treatment-resistant diaper rash.A variant of psoriasis called guttate psoriasis (“droplet-like”) may be the first manifestation in children. The lesions are 2 mm to 1 cm in diameter and generally are distributed symmetrically over the trunk and proximal aspects of the extremities. Two thirds of patients who present with guttate psoriasis have a history of an upper respiratory tract infection or streptococcal disease 1 to 3 weeks prior to the onset of rash. Throat or perianal cultures should be obtained in children who have guttate psoriasis. A particularly helpful finding in psoriasis is the Koebner phenomenon, which is when lesions appear at sites of local injury, such as a cut or scrape. The Koebner phenomenon, like the Auspitz sign, is not pathognomonic for psoriasis, but its presence is useful in establishing the diagnosis.The susceptibility to develop psoriasis is inherited, but the exact pattern of inheritance is more complex than simple mendelian genetics. Psoriasis has a strong association with the human leukocyte antigen locus. Recent studies have identified two subtypes of the plaque type, nonpustular form of psoriasis. Although the clinical lesions are indistinguishable, the inheritance is quite different. Type I has an age of onset younger than 40 years and is much more likely to affect a first-degree relative than in type II disease in which the onset is after age 40. Inheritance of psoriasis in children is highest in those who have type I psoriasis and demonstrate the B13 and A2 haplotype in addition to Cw6.Yet-to-be-discovered information about specific T-cell subsets and a variety of cytokines may yield the key to more effective therapy for this chronic disease. Of particular importance in childhood is the role of bacterial superantigens in the development of guttate psoriasis.The treatment of psoriasis is challenging, particularly in children,because therapeutic options are limited. For mild-to-moderate disease,emollients (moisturizers) and topical corticosteroids are often sufficient. Bland emollients, such as petroleum jelly, are inexpensive and easy to use. They alone may improve psoriasis by 40%. Low-to-medium potency topical corticosteroids may be insufficient for control, necessitating the use of potent agents, although they carry a significant risk for tachyphylaxis and local atrophy. They must be used carefully, ideally on an intermittent basis and with close clinical monitoring.Tar and anthralin are age-old agents that may be very helpful in childhood psoriasis. Unfortunately, their odor and mess can reduce compliance significantly.An important new topical agent is calcipotriene, a vitamin D analog. Available in the United States for the past 3 years, it has provided an excellent alternative to topical corticosteroids. Although it has not yet been approved by the United States Food and Drug Administration for use in children, early reports from Europe suggest that it is safe if used on a limited surface area with monitoring of calcium metabolism.Other treatment modalities available for patients who have severe or resistant disease include phototherapy, immunotherapy, and retinoids. Methotrexate at a dose of 0.2 to 0.4 mg/kg once a week for 31.2 to 46.4 weeks resulted in a post-therapy disease-free state of 14.4 to 16.8 weeks in children. Cyclosporin can clear severe adult psoriasis and psoriatic arthritis, but its safety and utility in children has yet to be determined.Childhood psoriasis can cause serious problems with peer relationships and have a significant financial impact on the family. Pediatricians and dermatologists often can control this chronic disease with family education, counseling, and a willingness to explore therapy with a combination of agents.

Genetics of psoriasis

I t has long been known that psoriasis has an important genetic component; however, since the advent of large-scale genetic studies, it has become clear that the genetic basis of psoriasis is far from simple. Many modes of inheritance have been proposed and rejected, thereby making it difficult for the practitioner who desires to counsel patients. This chapter provides a review of the pertinent literature on the inheritance of psoriasis. In the following section, summaries of the different studies are grouped according to the major characteristics of the study. Comments, when felt to be appropriate for purposes of genetic counseling, will be given directly afterwards. The last section presents a brief overview and a discussion of the implications for genetic counselling.

Immunogenetic profile of psoriasis vulgaris: association with haplotypes A2,B13,Cw6,DR7,DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201.

Psoriasis vulgaris is a skin disease with an immunological and genetic background present in 1-3% of the population. We studied the genetic susceptibility to psoriasis vulgaris in Finns with serological HLA typing and genomic HLA class II typing of the DQ and DP loci to evaluate the risk of developing psoriasis. The haplotypes most frequently distinguishing between psoriatics and controls were those that carried Cw6 (P < 10(-8)), DQA1*0201 (P = 9.3 x 10(-6)) and DR7 (P = 3.9 x 10(-5)). The two most frequent marker haplotypes were A2,B13,Cw6,DR7, DQA1*0201 and A1,B17,Cw6,DR7,DQA1*0201, which were not found among the control subjects. A deficit of haplotype B8,DR3,DQ2 (2 out of 124 in the patients versus 15 out of 106 in the controls, P = 1.5 x 10(-4)) was found, and this was in accordance with a slightly decreased frequency of DQA1*0501 (P = 3.1 x 10(-2)), which was usually linked with this haplotype. These results stimulate the research for a genetic resistance factor in psoriasis. Thus, this report sheds further light on the immunogenetic background of psoriasis in Finland. We conclude that the inheritance of psoriasis has a polygenic mode, in which the Cw6,DR7,DQA1*0201 combination seems to be important (P = 7.5 x 10(-7), relative risk 24.4, aetiological factor 0.29).

Molecular biology of psoriasis and its future management

Psoriasis is a chronic inflammatory multifactorial disease and the precise molecular defects causing psoriasis remain unclear; but a genetic predisposition and environmental factors are involved in the pathogenesis. A strong genetic component is found in certain individuals and the inheritance of psoriasis can be classified as autosomal dominant with variable penetrance. Clinically, psoriasis represents a collection of similar disorders with a variable phenotype, making investigation at the molecular level extremely complex. Lesions are characterized by hyperproliferation and abnormal epidermal differentiation, together with a strong inflammatory and immunological component. However, studies over the last 20 years have failed to find molecular alterations that are either specific to the psoriatic lesion or characteristic of uninvolved skin. Trauma, stress and chemicals are all known to precipitate psoriasis in susceptible individuals, but the molecular mechanisms are not understood. The accumulation of inflammatory cells in the epidermis and altered dermal vessels are major characteristics, and these changes are driven by release of cytokines and growth factors. Many investigations have shown that the process of epidermal differentiation in the lesion is aberrant. Increased transit time of cells through the epidermis combined with a shift to the ‘hyperproliferative state’ prevents the keratinocyte from completing the preprogrammed molecular events necessary for normal terminal differentiation. Calcium and its binding proteins are important in terms of providing the driving force for epidermal differentiation, and vitamin D, analogues have proved to be useful therapeutic agents in psoriasis. However, while they do reduce proliferation and stimulate epidermal differentiation, the precise mechanisms by which these agents work is also unknown although they do affect T-helper cell populations and may moderate the lymphocyte drive associated with the lesion. Every psoriatic patient presents an individual problem in terms of treatment as there is a wide variation in the type, extent, duration and history of the disease. However, while topical therapy with a variety of regimens is preferred, difficult cases do require more aggressive systemic therapy. It is indisputable that a further understanding of the molecular pathogenesis of psoriasis, the identification of genes linked to the condition and an appreciation of how uninvolved psoriatic skin differs from normal will have an impact on both how we view and treat this disfiguring skin disorder. Only when we have a complete picture of the events that initiate and drive the psoriatic lesion will we be able to develop effective regimens to control this condition. (J Derninfol Trent ( 1996) 7 (Suppl

Allelic instability in the mitosis model and the inheritance of psoriasis

Background : Allelic instability in mitosis has been proposed as a model for dominantly inherited diseases. Objective : Our purpose was to analyze our own and published data on the inheritance of psoriasis according to the predictions of the allelic instability-in-mitosis model. Methods : Frequency of psoriasis in father, mother, and siblings was extracted or calculated from data in the literature. Our case records were reviewed and supplemented by telephone or personal interviews when records were incomplete. Inheritance rates from each sex of parent were compared. Correlation between ages at onset in affected siblings was determined. Results : From our own data and the literature summary, the preponderance of inheritance from the father over the mother is statistically significant. A direct correlation exists between ages at onset in affected siblings. Age at onset in parent and child is also positively correlated. Average age at onset in parents is greater than in offspring. Conclusion : Both data from literature and our own data are in agreement with the predictions of the allelic instability in mitosis model. This provides evidence that an unstable gene may contribute to the genetics of psoriasis.

Of Genes and Antigens: The Inheritance of Psoriasis

Psoriasis is one of a number of autoimmune diseases that display significant HLA associations. In particular, individuals with onset of disease prior to 40 years of age display striking associations with HLA-Cw6 and are much more likely to have a positive family for psoriasis. However, only about 10% of Cw6-positive individuals develop disease, suggesting that other genetic and/or environmental factors must be involved. Several compelling lines of epidemiologic evidence indicate that psoriasis susceptibility is inherited, albeit not in a simple monogenic fashion, and that genetic, rather than environmental, factors are primarily responsible for the variability in inheritance of psoriasis. Taken together, these observations suggest that one or more loci in addition to HLA are necessary for the development of psoriasis. The number of additional loci is likely to be small, because i) the disease is very common ii) substantial excess risk of psoriasis is observed in first degree relatives, and iii) nevoid variants of psoriasis have been reported, suggestive of somatic mutation of a single gene during development. The substantial homogeneity of the psoriatic phenotype and the clear evidence for increased HLA association and heritability in juvenile onset disease indicate that despite its complexity, psoriasis is a common disease whose etiology is amenable to elucidation through the techniques of modern molecular genetics. J Invest Dermatol 103:150S-153S, 1994

Of Genes and Antigens: The Inheritance of Psoriasis.

Psoriasis is one of a number of autoimmune diseases that display significant HLA associations. In particular, individuals with onset of disease prior to 40 years of age display striking associations with HLA-Cw6 and are much more likely to have a positive family for psoriasis. However, only about 10% of Cw6-positive individuals develop disease, suggesting that other genetic and/or environmental factors must be involved. Several compelling lines of epidemiologic evidence indicate that psoriasis susceptibility is inherited, albeit not in a simple monogenic fashion, and that genetic, rather than environmental, factors are primarily responsible for the variability in inheritance of psoriasis. Taken together, these observations suggest that one or more loci in addition to HLA are necessary for the development of psoriasis. The number of additional loci is likely to be small, because i) the disease is very common ii) substantial excess risk of psoriasis is observed in first degree relatives, and iii) nevoid variants of psoriasis have been reported, suggestive of somatic mutation of a single gene during development. The substantial homogeneity of the psoriatic phenotype and the clear evidence for increased HLA association and heritability in juvenile onset disease indicate that despite its complexity, psoriasis is a common disease whose etiology is amendable to elucidation through the techniques of modern molecular genetics.

The Genetics of Psoriasis

The purpose of this study was to determine whether the inheritance of psoriasis is HLA linked. We studied 12 families with at least two siblings with psoriasis. We used a sib pair analysis comparing the HLA haplotypes in affected siblings of these families. Haplotype sharing was analyzed in 15 sib pairs; expected frequencies of haplotype sharing were estimated as 25% for HLA identity and 50% for haplotype identity. All sib pairs shared at least one haplotype and 13 of the 15 were HLA identical, compared with the expected frequency of four. These results suggest that at least one, and probably more, HLA-linked genes are implicated in the development of psoriasis.

The inheritance of psoriasis

The inheritance of psoriasis

The Inheritance of Psoriasis

The Inheritance of Psoriasis

HEREDITY AND PSORIASIS. STUDY OF A LARGE FAMILY.

The mode of inheritance of psoriasis in a large North Carolina kindred proved to be that of simple autosomal dominance with penetrance reduced to about 60%. No association was found between serum levels of uric acid and cholesterol and the occurrence of psoriasis in this kindred. The incidence of arthritis was 2.7% in the kindred, and there was no greater incidence among the psoriatic members of this kindred than the nonpsoriatic members. Rheumatoid factor was not detected in either the arthritic or nonarthritic members of this kindred by the latex agglutination technique. It is suggested that mutation at more than one locus and/or multiple alleles at the "psoriasis" locus may account for the conflicting reports concerning the inheritance of psoriasis.

Inheritance of psoriasis in a Utah kindred.

Psoriasis is a chronic inflammatory skin disorder of unknown etiology and inconstant course which constitutes about 6% of all new skin cases seen by dermatologists. 1 Of interest is the association of arthritis and psoriasis. This arthritis is characterized by absorptive phenomena usually of peripheral joints and has been considered to be a distinct form of joint disease. 2,3 The familial occurrence of psoriasis is well known and studies have described the inheritance as recessive, double recessive, and irregular dominant. Schamberg 4 reviewed 592 patients with psoriasis and reported a family occurrence of 13%. He concluded that there was no satisfactory evidence for genetic transmission of this disease. Steinberg et al. 5 examined 464 patients with psoriasis. The disease was present among the patient's siblings 4 times as often when one parent had psoriasis as when neither parent was affected. Six per cent of the patient's parents had psoriasis. Because