Large-scale epidemiological analysis of common skin diseases to identify shared and unique comorbidities and demographic factors.

Introduction: The utilization of large-scale claims databases has greatly improved the management, accessibility, and integration of extensive medical data. However, its potential for systematically identifying comorbidities in the context of skin diseases remains unexplored. Methods: This study aims to assess the capability of a comprehensive claims database in identifying comorbidities linked to 14 specific skin and skin-related conditions and examining temporal changes in their association patterns. This study employed a retrospective case-control cohort design utilizing 13 million skin/skin-related patients and 2 million randomly sampled controls from Optum's de-identified Clinformatics® Data Mart Database spanning the period from 2001 to 2018. A broad spectrum of comorbidities encompassing cancer, diabetes, respiratory, mental, immunity, gastrointestinal, and cardiovascular conditions were examined for each of the 14 skin and skin-related disorders in the study. Results: Using the established type-2 diabetes (T2D) and psoriasis comorbidity as example, we demonstrated the association is significant (P-values<1x10-15) and stable across years (OR=1.15-1.31). Analysis of the 2014-2018 data reveals that celiac disease, Crohn's disease, and ulcerative colitis exhibit the strongest associations with the 14 skin/skin-related conditions. Systemic lupus erythematosus (SLE), leprosy, and hidradenitis suppurativa show the strongest associations with 30 different comorbidities. Particularly notable associations include Crohn's disease with leprosy (odds ratio [OR]=6.60, 95% confidence interval [CI]: 3.09-14.08), primary biliary cirrhosis with SLE (OR=6.07, 95% CI: 4.93-7.46), and celiac disease with SLE (OR=6.06, 95% CI: 5.49-6.69). In addition, changes in associations were observed over time. For instance, the association between atopic dermatitis and lung cancer demonstrates a marked decrease over the past decade, with the odds ratio decreasing from 1.75 (95% CI: 1.47-2.07) to 1.02 (95% CI: 0.97-1.07). The identification of skin-associated comorbidities contributes to individualized healthcare and improved clinical management, while also enhancing our understanding of shared pathophysiology. Moreover, tracking these associations over time aids in evaluating the progression of clinical diagnosis and treatment. Discussion: The findings highlight the potential of utilizing comprehensive claims databases in advancing research and improving patient care in dermatology.

Dermatitis Herpetiformis and Celiac Disease Increase the Risk of Bullous Pemphigoid.

Bullous pemphigoid (BP) and dermatitis herpetiformis (DH) are autoimmune bullous skin diseases. DH has been described to evolve into BP and the two diseases can have overlapping clinical appearances and diagnostic findings, but the association between DH and BP has not previously been studied in a large population. To evaluate DH and celiac disease as risk factors for BP, we conducted a retrospective case-control study of patients with BP and matched controls with basal cell carcinoma diagnosed in Finland between 1997 and 2013. A total of 3,397 patients with BP and 12,941 controls were included in the study. Forty-one (1.2%) BP patients and 7 (0.1%) controls had preceding DH. Diagnosed DH increased the risk of BP 22-fold (odds ratio = 22.30; 95% confidence interval = 9.99-49.70) and celiac disease 2-fold (odds ratio = 2.54; 95% confidence interval = 1.64-3.92) compared to controls. Eighteen (43.9%) of the patients who had DH and subsequent BP had bought dapsone during the 2 years prior to their BP diagnosis. Mean time between diagnosed DH and BP was 3 years. We conclude that diagnosis of DH is associated with a striking increase in the risk for BP.

Management of dermatitis herpetiformis.

The major treatment strategies for DH are gluten restriction or medical treatment with sulfones. Control of the cutaneous manifestations, but not the gastrointestinal changes, is rapid with dapsone. In addition to control of the cutaneous signs and symptoms of DH, dietary gluten restriction also induces improvement of gastrointestinal morphology and is possibly protective against the development of lymphoma.

Assessing the role of HLA-linked and unlinked determinants of disease.

The relationship between increased risk in relatives over population prevalence (lambda R = KR/K) and probability of sharing zero marker alleles identical by descent (ibd) at a linked locus (such as HLA) by an affected relative pair is examined. For a model assuming a single disease-susceptibility locus or group of loci tightly linked to a marker locus, the relationship is remarkably simple and general. Namely, if phi R is the prior probability for the relative pair to share zero marker alleles identical by descent, then P (sharing 0 markers/both relatives are affected) is just phi R/lambda R. Alternatively, lambda AR, the increased risk over population prevalence to a relative R due to a disease locus tightly linked to marker locus A, equals the prior probability that the relative pair share zero A alleles ibd divided by the posterior probability that they share zero alleles ibd, given that they are both affected. For example, for affected sib pairs, P (sharing 0 markers/both sibs are affected) = .25/lambda S. This formula holds true for any number of alleles at the disease locus and for their frequencies, penetrances, and population prevalence. Similar formulas are derived for sharing one and two markers. Application of these formulas to several well-studied HLA-associated diseases yields the following results: For multiple sclerosis, insulin-dependent diabetes mellitus, and coeliac disease, a single-locus model of disease susceptibility is rejected, implying the existence of additional unlinked familial determinants. For all three diseases, the effect of the HLA-linked locus on familiality is minor: for multiple sclerosis, it accounts for only a 2.5-fold increased risk to sibs over the population prevalence, compared to an observed value of 20; for coeliac disease, it accounts for approximately a 5.25-fold increased risk to sibs, while the observed value is on the order of 60; for insulin-dependent diabetes mellitus, it accounts for a 3.42-fold increased risk in sibs, while the observed value is 15. In all cases, the secondary determinants must be outside the HLA region. For tuberculoid leprosy, an unlinked familial determinant is also implicated (increased risk to sibs due to HLA = 1.49; observed value = 2.38). For hemochromatosis and Hodgkin's disease, there is little evidence for HLA-unlinked familial determinants. With this formula, it is also possible to examine the hypothesis of pleiotropy versus linkage dis-equilibrium by comparing lambda AS with the increased risk to sibs due to the associated allele(s).(ABSTRACT TRUNCATED AT 400 WORDS)

[Granulomatous hepatitis. Etiologic study of 107 cases (author's transl)]. / Hepatitis granulomatosa, estudio etiológico de 107 casos.

An etiologic study was made of 107 cases of granulomatous hepatitis which were observed in a Department of Internal Medicine between January, 1971 and December, 1977 (excluding the hepatobiliary diseases). The most common etiology was tuberculosis (30 cases, 28 percent) followed by sarcoidosis (19 cases, 17.7 percent), Mediterranean exanthematous fever (13 cases, 12.1 percent), brucellosis (8 cases, 7.4 percent) typhoid fever (7 cases, 6.5 percent) and the idiopathic forms (8 cases, 7.4 percent). A lower rate of incidence was among Hodgkin's disease, toxoplasmosis, adenocarcinomas, leprosy, and those of unknown etiology, classified in this way because the study and follow-up of the patients could not be completed. There were, moreover, individual cases caused by mononucleosis, BCG reaction, hypogammaglobulinemia, celiac disease, and temporal arteritis. From a clinical point of view 50 percent of the patients had hepatomegaly and moderate disturbance of the liver enzymes. The most important enzymatic increases were detected in the cases caused by brucellosis; in the cases which were secondary to sarcoidosis the liver enzymes were normal. A comparison is established between the etiologic incidence of the present series and of others published in the literature. The causes and diagnostic problems of this type of lesion are discussed.

Reaction to Kveim test material in sarcoidosis and other diseases.

81 patients, 24 with sarcoidosis and the remainder with various other diseases, were tested with three batches of Kveim material prepared from the same spleen. Positive Kveim tests were observed in sarcoidosis, tuberculosis, Hodgkin's disease, ulcerative colitis, rheumatoid arthritis, and Weber-Christian disease. These results show that a positive Kveim reaction to the material under test was not specific to sarcoidosis.