Use of oral immunosuppressive drugs in the treatment of atopic dermatitis in the Netherlands.

BACKGROUND: Although atopic dermatitis (AD) is a very common skin disease, data on the percentage of patients with really difficult-to-treat AD are scarce. From socio-economic perspective, it is important to have more insight into these numbers, as new very effective, but expensive, treatment options will be available in the near future for difficult-to-treat AD. Estimating the number of patients with AD using oral immunosuppressive drugs can give an impression of the percentage of difficult-to-treat patients in the total AD population. OBJECTIVE: To give an overview of the use of oral immunosuppressive drugs in patients with AD in the Netherlands. METHODS: Prescription data of oral immunosuppressive drugs in the Netherlands were extracted from a pharmaceutical database (NControl) containing data of 557 million prescriptions and 7.2 million patients. An algorithm, based on the WHO Anatomical Therapeutic Chemical (ATC) codes, was used to identify patients with AD. The prescription of oral immunosuppressive drugs in patients with AD between 1 January 2012 and 1 January 2017 was evaluated. RESULTS: Based on the algorithm, 65 943 patients with AD were selected. 943 patients with AD (1.4%) used cyclosporine A, methotrexate, azathioprine or mycophenolic acid. Methotrexate was most commonly used, followed by azathioprine and cyclosporine A. A switch in medication was rarely seen. In the evaluation period, a decrease in the prescription of cyclosporine A was seen, together with an increase in the prescription of methotrexate. In 31% of the patients who stopped treatment, the discontinuation took place within the first months of treatment. CONCLUSION: In this study population, 1.4% of the patients with AD used oral immunosuppressive drugs for their eczema in a 5-year period. Methotrexate was the most commonly used systemic drug in the Netherlands for the treatment of AD.

Thiopurine metabolite levels in patients with atopic dermatitis and/or chronic hand/foot eczema treated with azathioprine.

BACKGROUND: Azathioprine is frequently used in severe eczema. It is converted in the liver into active metabolites, including 6-thioguanine nucleotide (6-TGN) and methylated 6-methylmercaptopurine (6-MMP). In the past, the therapeutic potential of azathioprine may have not been fully utilized. Recent investigations on inflammatory bowel disease have led to a better understanding of azathioprine metabolism and optimizing treatment. OBJECTIVE: To investigate whether measuring thiopurine metabolites in circulation can improve the effectiveness and safety of azathioprine treatment in patients with atopic dermatitis and/or chronic hand/foot eczema. METHODS: Azathioprine metabolite levels were measured in eczema patients during maintenance treatment (Part I) and dose escalation (Part II). Clinical effectiveness, hepatotoxicity, and bone marrow suppression were analyzed and TPMT genotype was assessed. RESULTS: A wide variation in metabolite levels in all dose groups was observed. In Part I (32 patients), there were no significant differences in 6-TGN levels between clinical responders and non-responders (p = .806). No hepatoxicity or myelotoxicity was observed. In Part II, all 6-TGN and 6-MMP levels increased during dose escalation. Hypermethylation was observed in 2/8 patients. CONCLUSION: For individual eczema patients treated with azathioprine, routinely measuring 6-TGN and 6-MMP can be helpful in optimizing azathioprine dose, improving clinical effectiveness, and preventing side effects.

Is there an increased risk of cervical neoplasia in atopic dermatitis patients treated with oral immunosuppressive drugs?

BACKGROUND: Oral immunosuppressive drugs are frequently prescribed in young women with atopic dermatitis (AD). Immunocompromised patients may have a higher risk of developing high-risk HPV infections, cervical intra-epithelial neoplasia (CIN) and cervical carcinoma. Most literature on patients using oral immunosuppressive drugs is available in organ transplant patients. Literature on the risk of developing cervical carcinoma in AD patients treated with oral immunosuppressive drugs is lacking. At this moment, there is no clear guideline/consensus on this topic, but in daily practice, questions arise concerning whether this risk is increased and whether more intensive screening in women using immunosuppressive drugs should take place. OBJECTIVE: To investigate the occurrence of cervical carcinoma in women with AD treated with oral immunosuppressive drugs. METHODS: In this retrospective cohort study in two university medical centres in the Netherlands, all female adult AD patients receiving oral immunosuppressive drugs (cyclosporine A, azathioprine, methotrexate, mycophenolate mofetil, enteric-coated mycophenolate sodium and extended release tacrolimus) for more than 2 months between 1989 and 1 January 2014 were included. Patient files in the national histopathology register were screened for PAP3a, CIN I, CIN II, CIN III and cervical carcinoma. RESULTS: A total of 257 female AD patients with one or more treatment episodes from 1989 until 1 January 2014 were identified and included in this study. In 189 patients (73.5%), results of cervical examination were reported in the national histopathology database. Median total duration of treatment in these 189 women was 407.0 days (IQR 243.0-940.0). No cervical carcinoma during or following immunosuppressive therapy was found in our patient group. CONCLUSIONS: No intensified screening programme for cervical neoplasia seems necessary for women with AD using oral immunosuppressive drugs.

Guttate psoriasis triggered by perianal streptococcal infection.

The association of guttate psoriasis (GP) with streptococcal pharyngitis is well accepted. However, less is known about the association with perianal streptococcal infection. We report a case of a 19-month-old boy with GP after a preceding perianal streptococcal dermatitis, with no clinical signs of a streptococcal pharyngitis. Treatment with phenethicillin was given together with mometasone ointment. After 4 weeks, the perianal redness was reduced and the psoriasis had improved significantly. A review of the literature revealed nine previous case reports, comprising a total of 15 patients. In all cases, the perianal dermatitis and the GP improved after treatment with oral antibiotics, sometimes in combination with topical corticosteroids. We conclude that in cases of GP in children, the perianal area must be examined for streptococcal infection.

Ten years experience with oral immunosuppressive treatment in adult patients with atopic dermatitis in two academic centres.

BACKGROUND: There is a lack of information on the use oral immunosuppressive drugs in atopic dermatitis (AD) daily practice. OBJECTIVE: A 10-years overview of the use of oral immunosuppressive drugs in patients with severe AD. METHODS: Medical charts of patients with AD, who received oral immunosuppressive drugs at the Academic Medical Center Amsterdam and in the University Medical Center Utrecht between January 2001 and January 2011, were analysed. Particular attention was paid to patient characteristics, prior treatment, prescribed oral immunosuppressive drugs, the order of use, doses and treatment durations and reasons for discontinuation of treatment. RESULTS: Of 334 patients [53% male, mean age at start of an oral immunosuppressive drug 36.9 years (SD 13.6)] with AD received oral immunosuppressive treatment of which 102 (31%) participated in clinical trials. Cyclosporine A (CyA) was given in 80% of the patients, mycophenolate mofetil or enteric-coated mycophenolate (MMF/EC-MPS) in 31%, azathioprine (AZA) in 14%, methotrexate (MTX) in 11%, systemic glucocorticosteroids in 7% and systemic tacrolimus in 5%. In these academic centra, CyA was the first choice oral immunosuppressive in 252 patients. Reasons for discontinuation of oral immunosuppressive drugs were controlled AD disease, ineffectiveness and adverse events. CONCLUSION: Various types of oral immunosuppressive drugs have been used over the past 10 years for the treatment of severe AD with a prominent first choice for CyA. Adverse events and ineffectiveness were frequent reasons for discontinuation. A prospective database of patients using oral immunosuppressive treatments in daily practice will give more insight in the effectiveness and safety and may help to formulate future recommendations.

Photo(chemo)therapy in the management of atopic dermatitis: an updated systematic review with implications for practice and research.

BACKGROUND: Photo(chemo)therapy is a common treatment modality in patients with atopic dermatitis (AD), but evidence on its effectiveness has not been recently systematically reviewed. OBJECTIVES: To evaluate the effect of treatment with photo(chemo)therapy in patients with AD and to make treatment recommendations on basis of the evidence. METHODS: We performed an electronic literature search in MEDLINE (OVID), EMBASE (OVID), the Cochrane Central Register of Controlled Trials (CENTRAL), Global Resource of EczemA Trials (GREAT) and prospective trial registers, complemented with a search of PubMed to find recent studies not yet available in OVID MEDLINE. All randomized controlled trials (RCTs) on phototherapy for the treatment of AD were considered for data extraction. RESULTS: Nineteen studies were included (905 participants). The identified RCTs were generally clinically and qualitatively heterogeneous. Therefore a formal meta-analysis was not feasible. Conclusions must be drawn carefully because of small sample sizes, varying study quality and sometimes the absence of direct comparisons, but on the basis of the included evidence, ultraviolet (UV) A1 and narrowband (NB)-UVB appeared the most effective treatment modalities for the reduction of clinical signs and symptoms. No difference between high-dose UVA1 and medium-dose UVA1 was seen. UVAB was shown to be more effective than UVA and broadband-UVB for the improvement of clinical symptoms, but not compared with UVA1. Other effective treatment options include full-spectrum light, psoralen plus UVA and balneophototherapy. No serious side-effects were reported. CONCLUSIONS: Phototherapy can be a valid therapeutic option for patients with AD. Based on the results of this review, preference is given to UVA1 and NB-UVB. Further well-designed, adequately powered RCTs are required.