[Brain teasers in pruritus-when laboratory tests will guide you]. / Kniffelige Fälle ­ Wann bringt die Labordiagnostik eine Lösung?

Chronic pruritus is a symptom of many systemic diseases. In contrast to dermatological pruritus, there are no primary changes in skin appearance. Establishing the correct diagnosis in these cases can be quite challenging. In some instances, laboratory tests can be helpful. This report highlights the importance of specific and target-orientated laboratory tests in four patients with chronic pruritus due to systemic diseases.

[Pruritus in systemic diseases : Common and rare etiologies]. / Pruritus bei systemischen Erkrankungen : Häufiges und Seltenes.

Chronic pruritus is a symptom of various internal disorders. In contrast to dermatological diseases, pruritus does not present with primary skin alterations in these patients. However, intense scratching my cause secondary skin changes such as abrasion, excoriation, prurigo nodularis, or in rare cases even scarring. The most common internal causes for chronic pruritus are chronic kidney disease, hepatobiliary, and hematological disorders as well as adverse drug reactions. Pruritus is less commonly seen in patients with endocrine or metabolic diseases, malabsorption syndromes, infectious diseases, and solid tumors. The pathogenesis of pruritus in these disorders remains largely elusive, albeit first insights have been gained for uremic and cholestatic pruritus. Antipruritic treatment is therefore symptomatic in most cases and may represent a clinical challenge. The calcium channel blockers gabapentin and pregabalin have the best proven efficacy in chronic kidney disease associated pruritus. In Japan, nalfurafine, a κ-opioid receptor agonist, has been licensed for this indication. UVB light may also attenuate uremic symptoms. In patients suffering from hepatobiliary disorders the sequestrant cholestyramine and the enzyme inducer rifampicin are effective. Furthermore, bezafibrate, the µ­opioid receptor antagonists and, in Japan, nalfurafine may be used to ameliorate cholestatic pruritus. So far, no randomized controlled trials have been performed for chronic itch in other internal disorders. Antipruritic treatment is symptom-based with a focus on the effective therapy of the underlying disease.

The course of chronic itch in hemodialysis patients: results of a 4-year follow-up study of GEHIS (German Epidemiological Hemodialysis Itch Study).

BACKGROUND: Chronic itch (CI) is a frequent symptom in hemodialysis (HD) patients. Previous studies demonstrated great impairments of general well-being and health-related quality of life (HRQOL) as well as a higher mortality in those suffering from CI. OBJECTIVE: The German Epidemiological Hemodialysis Itch Study (GEHIS) is a representative cohort of HD patients in Germany. All patients were followed up 4 years later. The current analyses present data on the course of CI in HD patients, its associated factors including comorbidities, laboratory values and HRQOL. METHODS: We assessed sociodemographic data, routine laboratory values, comorbidities, HRQOL (SF-12), depression and anxiety (HADS), sleep (duration and quality) and in those suffering from CI characteristics, intensity of CI and itch-related quality of life (ItchyQoL). Those with CI were offered a dermatological examination and CI was classified according to the IFSI classification. Patients were asked if they had consulted a physician about CI. RESULTS: Of the patients who had suffered from CI in 2013 (n = 234), 90.5% (212) patients could be followed up. About 36.3% (n = 85) had died, 9.8% (n = 23) had received a kidney transplant in the meantime. A total of 52 HD patients still suffered from CI, in 52 CI had stopped. Those patients still suffering from CI (n = 52) reported a higher mean itch intensity, lower ItchyQoL, higher levels of anxiety and a lower mean sleeping time in 2013. On the other hand, those who did not suffer from CI anymore showed a significant increase of HRQOL compared to 2013. There was no significant difference in dialysis characteristics and laboratory values except for albumin. Only a minority of patients in HD had consulted a dermatologist because of CI (29.9%). CONCLUSION: Our data demonstrate that CI is a persisting symptom in 50% of the HD patients and when it disappears HRQOL recovers. We confirm that CI is a disregarded symptom in HD patients.

[Pruritus in elderly people-an interdisciplinary challenge]. / Pruritus im Alter ­ eine interdisziplinäre Herausforderung.

Due to demographic change, especially in Western countries with increasing life expectancy and a continuously increasing number of elderly, chronic pruritus (CP) is more and more observed in clinical practice. CP in elderly may present with specific pruritic skin diseases, as chronic prurigo (nodular form) and can also occur in unaffected, normal looking skin. CP in elderly remains a challenge. Especially CP without any skin lesions is a major diagnostic and therapeutic challenge. Due to the increasing prevalence of malignant diseases in elderlies, paraneoplastic pruritus is also an important differential diagnosis. Treatment depends on the mobility of the patient which determines if and which topical agents can be used and if ultraviolet phototherapy can be administered. There are a number of topical and systemic medications, which must be selected according to existing comorbidities, possible drug interactions, and the patient's compliance as well as possible side effects such as cognition and sedation. All this may hamper treatment of CP in elderly.

Lower prevalence of chronic itch in haemodialysis patients on loop diuretics: results from GEHIS (German Epidemiological Hemodialysis Itch Study).

BACKGROUND: Chronic itch (CI) is a very tormenting symptom in haemodialysis (HD) patients. GEHIS (German Epidemiological Hemodialysis Itch Study) is a representative cross-sectional study showing that current chronic itch (CI) affects 25.2% of haemodialysis (HD) patients. OBJECTIVE: We investigated drug intake and possible associations between CI and medications of HD patients. METHODS: Eight hundred and sixty HD patients from a randomly selected cluster sample of 25 dialysis units (GEHIS) in Germany were investigated. Statistical analyses were performed using R (version 3.3.0) for Windows. Logistic regression was used to identify influential covariates for prevalence of chronic itch and intensity of itch. RESULTS: Taking loop diuretics (furosemide, torasemide) was significantly negatively associated with the occurrence of CI in HD patients meaning that those who had received any type of loop diuretics were significantly less likely to suffer from less CI compared to those who had not taken them. There were no associations of CI with other medications. No correlation was detected between the intensity of itch and the intake of loop diuretics or any other medication. CONCLUSION: Loop diuretics may have an impact on the development of CI in HD patients. As it is most likely that a multifactorial origin may explain CI in HD, future research should also focus on the role of loop diuretics in CI, both on a clinical as well as on a molecular level.

[Pruritus in systemic diseases : Common and rare etiologies]. / Pruritus bei systemischen Erkrankungen : Häufiges und Seltenes.

Chronic pruritus is a symptom of various internal disorders. In contrast to dermatological diseases, pruritus does not present with primary skin alterations in these patients. However, intense scratching may cause secondary skin changes such as abrasion, excoriation, prurigo nodularis, or in rare cases even scaring. The most common internal medicine causes for chronic pruritus are chronic kidney disease, hepatobiliary and hematological disorders as well as adverse drug reactions. Pruritus is less commonly seen in patients with endocrine or metabolic diseases, malabsorption syndromes, infectious diseases and solid tumors. The pathogenesis of pruritus in these disorders remains largely elusive, albeit preliminary insights have been gained for uremic and cholestatic pruritus. Antipruritic treatment is therefore symptomatic in most cases and may represent a clinical challenge. The calcium channel blockers gabapentin and pregabalin have the best proven efficacy in chronic kidney disease-associated pruritus. In Japan nalfurafine, a κ-opioid receptor agonist, has been licensed for this indication. UVB light may also attenuate uremic symptoms. In patients suffering from hepatobiliary disorders the sequestrant cholestyramine and the enzyme inducer rifampicin are effective. Furthermore, µ­opioid receptor antagonists and sertraline may be used to ameliorate cholestatic pruritus. So far, no randomized controlled trials have been performed for chronic itch in other internal medicine disorders. Antipruritic treatment is mainly based on effective therapy of the underlying disease.

[Treatment of chronic itch in systemic disease. Current standards]. / Therapie des Pruritus bei inneren Erkrankungen. Was ist gesichert?

Chronic itch (CI) is a frequent and sometimes tormenting symptom in many skin and systemic diseases. In systemic diseases, it mostly appears on primarily unaffected skin. As a sequelae of intense scratching, secondary skin lesions such as excoriations, scars, and prurigo nodularis may occur. Due to the lack of valid pathogenetic concepts and good clinical trials, the therapy of CI remains mostly symptomatic. In Europe almost all drugs used to treat CI are not approved for this indication. CI is frequent in patients with chronic kidney diseases in advanced stages. Gabapentin and pregabalin, anticonvulsants, and centrally acting calcium channel blockers have been shown to exert a profound effect in CI. Furthermore, UVB phototherapy has been proven to attenuate pruritus in uremic patients. Randomized controlled studies have recently shown that nalfurafine, a κ-opioid receptor agonist, is able to ameliorate itch in patients with uremic itch. In patients suffering from cholestatic itch, the anion exchange resin colestyramine and rifampicin are effective antipruritic drugs. Furthermore, µ-opioid receptor antagonists and sertraline may be used to alleviate CI in hepatic diseases. In refractory cases, naso-biliary drainage or albumin dialysis are effective invasive procedures. For the treatment of chronic itch in hematological diseases no controlled trials have been performed so far. The mainstay in these cases is to treat the underlying disease.

[Prurigo nodularis: its association with dermatoses and systemic disorders]. / Prurigo nodularis bei Dermatosen und systemischen Erkrankungen.

BACKGROUND: Prurigo is seen in various dermatological diseases, but also in systemic and neurological diseases. OBJECTIVES: Which diseases in dermatology, internal medicine and neurology are linked to prurigo nodularis? MATERIAL AND METHODS: We describe the various entities that are associated with prurigo and discuss pathogenetic and therapeutic implications. RESULTS: In dermatology prurigo nodularis is most frequently seen in atopic dermatitis, but also in cutaneous lymphomas, mycobacterial skin infections and bullous diseases. Among systemic diseases, prurigo nodularis frequently is associated with pruritus of chronic renal or hepatic diseases. Prurigo nodularis is also seen in hematological and metabolic diseases (such as solid tumors, lymphoma, diabetes mellitus). The pathophysiology of prurigo is only partly understood. Treatment of prurigo nodularis is often challenging and a multimodal approach is advisable. CONCLUSION: Prurigo nodularis is a skin manifestation of chronic pruritus caused by various diseases in dermatology, internal medicine and neurology. An interdisciplinary approach should be taken for diagnosis and therapy.

[Clinical features and prurigo nodularis in nephrogenic pruritus]. / Klinische Charakteristika und Prurigo nodularis bei nephrogenem Pruritus.

BACKGROUND: Nephrogenic pruritus (NP) is a well-known associated symptom in patients with chronic renal failure. The aim of the present study was to make a detailed dermatological analysis including distribution of excoriations and their correlation with pruritus characteristics. PATIENTS AND METHODS: Data on a total of 17 patients with NP (14 males, mean 65.4 ± SD 14.3 years) were subjected to retrospective analysis. Most of the patients developed NP after start of kidney disease; however, in 20 % of the patients, there was premonitory appearance of the symptom 18 months (median) earlier. A majority of patients reported neuropathic symptom qualities (burning, stinging). In 94.1 % of patients xerosis was present; in 58.8 %, prurigo nodularis. The latter group of patients had a longer duration of pruritus as well as up to 10 years longer duration of renal disease than those without prurigo. RESULTS: Pruritus characteristics of NP show a wide variance without a clear profile that is useful for clinical diagnosis. NP can occur premonitorily, and, if of long duration and with coexistent metabolic diseases, can develop into prurigo.

[Pruritus with systemic diseases]. / Pruritus bei inneren Erkrankungen.

Chronic itch is a frequent symptom not only associated with skin diseases. In a number of internal, neurological and psychiatric illnesses pruritus can be a prominent and distressing symptom. Diagnosis is frequently very cumbersome because pruritus in these diseases often does not cause any specific skin lesions. This report focuses on the most important internal disease entities causing pruritus and highlights the most successful diagnostic and therapeutic approaches.

[Clinical classification of chronic pruritus. Interdisciplinary consensus proposal for a diagnostic algorithm]. / Klinische Klassifikation von chronischem Pruritus. Interdisziplinärer Konsensusvorschlag für einen diagnostischen Algorithmus.

Chronic pruritus is a frequent symptom in dermatology caused by a variety of dermatologic, neurologic and other systemic diseases. For adequate, economically-appropriate medical care of patients with chronic pruritus, a clinical classification of pruritus which also serves as a diagnostic algorithm is necessary. Currently suggested classifications are etiologic and not helpful in daily clinical routine. The proposed clinical classification is oriented at the clinical appearance of the patients and differentiates between disorders with or without primary or secondary skin lesions.

Continuing CAPD after herniotomy.

There is still controversy as to whether PD-treatment can be safely continued after herniotomy (HT). Many nephrologists withhold PD-treatment for several weeks after HT in fear of dialysate leakage and/or hernia recurrence. We report on 12 patients (2 women, 10 men) in whom HT was performed either for umbilical (n = 6), inguinal (n = 6) or open processus vaginalis (n = 3). Surgery was performed according to the Lichtenstein method with insertion of a Marlex-mesh and ligation of the hernia sac. In all patients PD treatment was paused for the day of surgery and 1 to 3 days postoperatively, depending on RRF. Low volume (1.0 to 1.5 l) and high frequency exchanges (6 exchanges per day) were started for several days with a gradual reinstitution of the former PD-regimen within the next 2 to 4 weeks. All patients did well rapidly with no uraemia-or dialysis-related complications. No leakage and no hernia recurrence could be observed 3 months thereafter. None of the patients had to be haemodialysed intercurrently. In conclusion, continuing a modified regimen of PD-treatment after HT seems to be safe and comfortable for the patient.

Sustaining continuous ambulatory peritoneal dialysis after herniotomy.

Controversy still exists as to whether peritoneal dialysis (PD) treatment can be safely continued after herniotomy. Many nephrologists withhold PD treatment for several weeks after herniotomy for fear of dialysate leakage and hernia recurrence. Here, we report on 9 patients (2 women, 7 men) in whom herniotomy was performed for umbilical (n = 3), inguinal (n = 5), or cicatricial hernia (n = 2), or for open processus vaginalis (n = 2). Surgery was performed according to the Lichtenstein method with insertion of a polypropylene mesh and ligation of the hernia sac. In all patients, PD treatment was paused for the day of surgery and for 1-3 days postoperatively, depending on residual renal function. Over the next several days, low-volume (1.0-1.5 L), high-frequency (6 per day) exchanges were started. The patient's original PD regimen was gradually reinstated over the next 2-4 weeks. All patients recovered rapidly, with no uremia or dialysis-related complications. Particularly, no leakage and no hernia recurrence could be observed 3 months thereafter. None of the patients had to be hemodialyzed intercurrently. In conclusion, continuing a modified regimen of CAPD treatment after herniotomy seems to be safe, with excellent patient comfort.

P-glycoprotein-mediated transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin.

Digoxin is a drug with a narrow therapeutic index, which is substrate of the ATP-dependent efflux pump P-glycoprotein. Increased or decreased digoxin plasma concentrations occur in humans due to inhibition or induction of this drug transporter in organs with excretory function such as small intestine, liver and kidneys. Whereas particle size, dissolution rate and lipophilic properties have been identified as determinants for absorption of digitalis glycosides, little is known about P-glycoprotein transport characteristics of digitalis glycosides such as digitoxin, alpha-methyldigoxin, beta-acetyldigoxin and ouabain. Using polarized P-glycoprotein-expressing cell lines we therefore studied whether these compounds are substrates of P-glycoprotein. Polarized transport of digitalis glycosides was assessed in P-glycoprotein-expressing Caco-2 and L-MDR1 cells (LLC-PK1 cells stably transfected with the human MDR1 P-glycoprotein). Inhibition of P-glycoprotein-mediated transport of these compounds in Caco-2 cells was determined using the cyclosporine analogue PSC-833 (valspodar) as inhibitor of P-glycoprotein. No polarized transport was observed for ouabain. However, basal-to-apical transport of digitoxin, alpha-methyldigoxin and beta-acetyldigoxin was greater than apical-to-basal transport in Caco-2 and L-MDR1 cells. In Caco-2 cells net transport rates of these compounds were similar to those of digoxin (digoxin: 16.0+/-4.4%, digitoxin: 15.0+/-3.3%, beta-acetyldigoxin: 16.2+/-1.6%, alpha-methyldigoxin: 13.5+/-4.8%). Furthermore, polarized transport of these compounds could be completely inhibited by 1 microM PSC-833. In summary, these data provide evidence that not only digoxin, but also digitoxin, alpha-methyldigoxin and beta-acetyldigoxin are substrates of P-glycoprotein.

Containers for waste causing peritonitis in CAPD patients.

Fungal infection is a rare cause of peritonitis in patients on chronic peritoneal dialysis. In this population, fungi are found in less than 2 percent of all cases of primary episodes of peritonitis (1). More often, a primary bacterial peritonitis treated with antibiotic therapy leads to secondary fungal infection (2). Candida species cause 74.5% of the episodes of fungal peritonitis (2). The fungi invade the peritoneal cavity from the skin peri- or intraluminally through the catheter (3). Filamentous fungi are rare (4,5). Treatment of fungal peritonitis commonly consists of removal of catheter and antifungal drugs (3). Here we describe two cases of fungal peritonitis caused by mycelial fungi, where the source of the microorganism could be special containers used for biological waste, which are popular in Germany