Floor M. Garritsen

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

There is a lack of information on the use oral immunosuppressive drugs in atopic dermatitis (AD) daily practice.

Pregnancy and fetal outcomes after paternal exposure to azathioprine, methotrexate or mycophenolic acid: a critically appraised topic

A 35-year-old male patient with atopic dermatitis (AD) is being treated with mycophenolate mofetil (MMF). He and his female partner wish to have children. They wonder whether the use of MMF, or any of the other alternative oral immunosuppressive drugs to treat AD, will be a risk for the fetus and whether this medication should be discontinued. He searched on the internet and found that the use of MMF was contraindicated.

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.

Dupilumab in atopic dermatitis: rationale, latest evidence and place in therapy

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases. The prevalence of AD is increasing and is currently estimated at 10–20% in adults worldwide. In the majority of patients, AD can be adequately controlled with topical treatment or ultraviolet light therapy, but there is a high unmet need for effective and safe therapeutics in patients with more severe or difficult to treat AD. During the past decade, new advances in the understanding of the underlying immune pathogenesis of AD have led to the development of new, more targeted therapies. Dupilumab, a fully human monoclonal antibody targeting the interleukin (IL)-4 receptor α, thereby blocking the IL-4 and IL-13 pathway, is one of the first biologics that has been developed for AD. Dupilumab has shown promising results in phase III trials and has recently been approved by the US Food and Drug Administration and the European Commission for the treatment of moderate to severe AD. With the approval of dupilumab, we are entering a new era of biological therapeutics in AD management. The place of dupilumab should be established in the current treatment standards. Based on current treatment guidelines and experts’ opinions in the management of AD, we have built a proposal for a treatment algorithm for systemic treatment of AD in European countries.

Risk of Non-melanoma Skin Cancer in Patients with Atopic Dermatitis Treated with Oral Immunosuppressive Drugs

There is uncertainty about the risk of developing non-melanoma skin cancer (NMSC), including basal cell carcinoma and squamous cell carcinoma (SCC), in patients with atopic dermatitis (AD) treated with oral immunosuppressive drugs. A total of 557 patients with AD treated with these drugs in the University Medical Center Utrecht and Groningen, the Netherlands, were analysed. NMSC after oral immunosuppressive treatment was reported in 18 patients (3.2%). The standardized incidence ratio for developing SCC was 13.1 (95% confidence interval (95% CI) 6.5-19.7). Patients developing NMSC were older at the start of therapy (p<0.001) and data lock (p<0.001) compared with patients without NMSC. No significant differences were found in sex, cumulative days of oral immunosuppressive drugs and follow-up between these groups (p=0.42, p=0.88, and p=0.34, respectively). In interpreting these results it is important to include other factors, such as lack of association between treatment duration and tumour development and the long interval between treatment discontinuation and tumour development in some patients.

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

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.

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

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.

Lymphopenia in atopic dermatitis patients treated with oral immunosuppressive drugs

Abstract Introduction: Oral immunosuppressive drugs are commonly used in the treatment of atopic dermatitis (AD). In patients with autoimmune- and rheumatic diseases, these drugs have been associated with lymphopenia. Lymphopenia is related to an increased risk of opportunistic infections. The incidence of lymphopenia in patients with AD treated with oral immunosuppressive drugs is yet unknown. Objective: To evaluate the occurrence of recurrent lymphopenia in patients with AD treated with oral immunosuppressive drugs and to make recommendations for screening in daily practice. Methods: Patients with recurrent lymphopenia (i.e. >5 times lymphocyte counts below 0.8 × 109/L) during treatment with oral immunosuppressive drugs were included from our immunosuppressive drugs database and further analyzed. Results: A total of 360 AD patients, treated with oral immunosuppressive drugs, were screened. A recurrent lymphopenia during treatment was found in 11 patients. In 8/11 patients, recurrent lymphopenia was observed during concomitant treatment with prednisone. No serious infections were observed. Conclusion: Lymphopenia is occasionally seen in AD patients treat with oral immunosuppressive drugs. Concomitant treatment with prednisone seems to be a risk factor. We suggest to include monitoring of lymphocyte counts in the standard follow-up for all AD patients treated with oral immunosuppressive drugs.

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

Abstract 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.