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analyzes the treatment of several special types of severe AD patients.
Atopic dermatitis (AD) is a common chronic, recurrent, inflammatory skin disease. Patients often have severe itching, which seriously affects their quality of life. According to the patient's severity of the condition, the step-by-step treatment model for choosing different drugs has been recognized by everyone. Most mild patients have better therapeutic effects, while some moderate to severe patients have poor treatment results. The emergence of biological agents and small molecule drugs in recent years have provided better and more choices for AD patients. However, the treatment of some special severe AD patients is still very challenging. For example, in special ages or physiological states such as infants, the elderly, pregnancy, etc., as well as pathological conditions such as tumors and infections, the choice of treatment methods for severe AD requires communication between doctors and patients and careful choice.
1 Infants and young children
Infants and young children have high prevalence of AD, and most of them have milder conditions. Use more moisturizer and topical glucocorticoids (TCS) to achieve good therapeutic effects. Because the child's family is afraid of hormone side effects and other reasons, the child has not received active and effective treatment, which may worsen the condition and develop moderate or even severe AD. At present, most of the instructions for domestic TCS preparations do not specify whether infants and young children are suitable for use. In China, the instructions for topical calcitase inhibitors (TCI) and Ceriborol ointment are clearly used for the treatment of AD in children aged 2 years and above [1-3]. In some countries, pimelimus cream or kerborol ointment is approved for the treatment of mild and moderate AD in infants and young children with 3 months of age and above [4,5]. Some experts believe that the correct use of non-hormonal anti-inflammatory drugs in the early stage can reduce the occurrence of severe AD in children. Duprilizumab is a better choice for moderate to severe AD that is ineffective in traditional treatments.
2 elderly
In a survey of about 20,000 AD patients abroad, it was found that nearly 10% of those older than 65 years old were [6]. Due to the possible existence of multiple chronic diseases, a high risk of potential infections or tumors, and the possibility of using multiple drugs, traditional drugs for treating severe AD (such as the system using glucocorticoids , cyclosporine, methotrexate , mycophenolic acid esters, azathioprine , etc.) have certain restrictions. In recent years, the new drug JAK inhibitor has a good effect on severe AD. Due to its short marketing period, long-term safety needs to be confirmed. Doctors and patients have certain concerns about their black box warnings. Ultraviolet light therapy has better efficacy and less side effects, but it is necessary to go to the hospital for frequent treatment. This is not a preferred treatment for older people, especially those with reduced mobility. In real-world studies, the biological agent Dupriliumab is safer for the treatment of severe AD in elderly people. Studies that lasted up to 52 weeks have also confirmed its efficacy (Figure 1) and safety. The efficacy of Dupriliumab used by elderly patients with AD (based on the EASI score) is similar to that of young people.
Figure 1: Changes in EASI, DLQI, S-NRS, and P-NRS scores during the 52-week treatment
***: p 0.0001; ns: No statistical significance
3
AD is one of the most common skin diseases during pregnancy, accounting for about 50% of all skin diseases. It often aggravates [8] during pregnancy. The main reasons for more susceptibility to AD during pregnancy are Th2 drift, increased psychological and physiological stress, and unwilling to take medication to treat it. AD during pregnancy can significantly affect the mother's quality of life and cause her to experience emotional changes such as anxiety. The mother has AD and the risk of neonatal sepsis, Staphylococcus aureus infection, herpetic eczema, and AD is increased in the offspring. If AD during pregnancy is ineffective after sufficient moisturizing treatment, TCS or TCI can be used. UV light therapy can be used even in severe cases. If the above traditional treatments are ineffective, systematic treatments are considered, such as cyclosporine and systemic glucocorticoids. If azathioprine has been used before pregnancy, you can continue to use it but the dose is halved (Figure 2) [8]. In recent years, multiple cases have reported that the use of primuluzumab for severe AD during pregnancy has good efficacy and no side effects on the fetus were found. The World Health Organization's individual safety report database (VigiBase) includes 37,848 reports of drug adverse reactions related to pulizumab worldwide. Only 36 cases occurred during pregnancy, puerperal period and perinatal period. The study found that the adverse reactions of drug were not related to pulizumab. The study concluded that the application of pulizumab during pregnancy seems to be a safer [9].
Figure 2: Treatment decision path for AD during pregnancy
4
Traditional severe AD treatment drugs (such as cyclosporine, methotrexate, mycophenolate, azathioprine, etc.) are all immunosuppressant , which has an inhibitory effect on multiple immune cells , and theoretically has a certain risk of inducing tumor incidence or aggravating tumor condition. The main mechanism of duprimuluzumab in treating AD is to inhibit signal transduction of IL-4 and IL-13, thereby inhibiting the type 2 inflammatory response that plays an important role in AD pathogenesis. It is not related to the anti-tumor immune pathway, so it may have no effect on the body's tumor immune response. There are literature reports that Primuzumab is used for the treatment of severe AD patients with tumors [10-12]. However, for cutaneous lymphomas misdiagnosed with AD, it has been reported that the use of prilizumab may accelerate the progress of cutaneous lymphoma, and even deaths occurred. Therefore, for elderly AD, especially those with atypical symptoms, skin lymphoma should be ruled out, and then consider applying priliumab to treat [13].
5
Report on the treatment of severe AD patients with viral hepatitis . Some literature reports that low doses of cyclosporine are used for the treatment of AD patients with hepatitis C or hepatitis B. There are also several cases of severe AD patients with pulizumab. The above treatments have good efficacy for AD and have no effect on viral hepatitis [14-16]. For severe AD combined with HIV or COVID-19, there are very few literatures for treating traditional immunosuppressants, and many clinical cases have been reported with priliumab. Some studies used duprimuluzumab to treat severe AD combined with HIV and followed up for 27 months. The rash continued to subside, the quality of life improved, the serum IgE level decreased to normal, and the HIV infection condition was stable. In a study of 442 AD patients with COVID-19, patients treated with duprimuluzumab had a lower risk of hospitalization than those treated with other topical medications and were also lower than those treated with systemic glucocorticoids and cyclosporine (no statistical significance) (Figure 3) [18].
Figure 3: Compared with AD patients who received duprimuluzumab, the risk of hospitalization for COVID-19 in AD patients who received topical medication or single traditional system treatment
6 Other
Cataldo Patrono et al. compared the efficacy and safety of AD patients with cancer, severe renal failure, viral hepatitis, neurological diseases, HIV infection and transplantation with ordinary AD patients. They found that the efficacy and safety of AD patients with duprimuluzumab were not significantly different from those with ordinary AD patients. A review shows that among many systematic treatments with viral or nonviral hepatitis, renal failure, malignant tumors and HIV infection comorbidities, as well as elderly AD patients, duprimulinumab is the first-line treatment [20].
In short, the treatment of severe AD, especially AD in special cases, is relatively difficult. According to current research, whether in special age or physiological states such as children, the elderly, pregnancy, or in pathological situations such as tumors and infections, duprimuluzumab is a treatment method with high efficacy and fewer side effects, providing a good treatment for our AD treatment in complex situations.
Expert Profile
Liu Sujun Professor
Deputy Chief Physician, PhD, Hangzhou Third People's Hospital
Chinese Rehabilitation Medical Association Dermatology Rehabilitation Professional Committee Children's Dermatology Group Member
Zhejiang Medical Association Dermatology Branch Children's Dermatology Group Member html
Allopathic branch of Zhejiang Medical Association Dermatology Group Member
Allopathic branch of Zhejiang Medical Association Scientific Research Management Branch of Zhejiang Medical Association
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[4M No.: MAT-CN-2225600; Approval time: October 2022]
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