A therapeutic challenge: managing severe atopic dermatitis with concurrent alpha-1-antitrypsin deficiency

Dear Editor:

Alpha-1-antitrypsin deficiency (DAAT) is a genetic disease characterized by low levels of alpha-1-antitrypsin. It is due to mutations in the SERPINA1 gene, which produces altered nonfunctioning forms of Alpha-1-antitrypsin (AAT) (1, 2). It can cause cirrhosis and pulmonary emphysema. We report a case of a patient with alpha-1-antitrypsin deficiency and moderate-to-severe atopic dermatitis (AD) with an exceptionally rapid response to dupilumab.

A 46-year-old woman was referred to our department by her Pneumologist for moderate-to-severe atopic dermatitis (basal scores: Eczema Area and Severity Index [EASI] 34, SCORing Atopic Dermatitis [SCORAD] 81, Body Surface Area [BSA] 51%, Investigator Global Assessment [IGA] 4, Visual Analogue Scale [VAS] for pruritus 10/10, Dermatology Life Quality Index [DLQI] 30, Patient Oriented Eczema Measure [POEM] 28) (Figure 1). Her medical history was significant for allergic asthma and pulmonary emphysema due to severe DAAT (Pi*S Matawa genotype). AAT levels were 44 mg/dl (laboratory range values 116–232 mg/dl). She had atopic dermatitis since childhood for which several cycles of oral prednisone and chronic application of topical high-potency corticosteroids had been used without adequate control.

Figure 1. Initial consultation. Physical examination revealed generalized involvement with erythema, xerosis, punctate excoriations, lichenization plaques and eczema.

Systemic treatment was considered given the severity of the disease and its high burden on the patient’s quality of life. Blood tests revealed abnormally high IgE levels (peaked at 24,000 kU/L)(laboratory range values 3–423Ul/ml) and IGRA was positive. Department of Infectious Diseases confirmed latent tuberculosis (TB) infection. Treatment with dupilumab was sought so as to minimize the risk of infection and reactivation of latent tuberculosis associated with other classical immunosuppressors and novel molecules (3, 4). As indicated by expert consensus, patients with latent TB should not be treated with JAK inhibitors or traditional systemic therapies for AD until latent TB is treated as per local guidelines (5). In patients with untreated latent TB, biologic therapies with proven efficacy in AD are the preferred option based on their mechanism of action. In fact, it has been hypothesized that biologics targeting the IL-13/IL-4Rα axis would not disrupt granulomas and, therefore, do not result in unchecked replication of TB (5). In addition, dupilumab could effectively inhibit Th2 signals and indirectly enhance Th1 responses to defense against intracellular pathogens (6).

An induction dose of 600 mg was started, followed by doses of 300 mg every two weeks. The patient showed a quickly improved dermatitis after dupilumab started (week 4: EASI 8, SCORAD 14, BSA 10%, IGA 2), VAS pruritus 7/10, DLQI 22, and POEM 19. Follow-up showed a complete improvement of AD at six months (EASI 1.3, SCORAD 3, BSA 0,5, IGA 1 VAS pruritus 4/10, DLQI 0, POEM 0; Figure 2). She reported no side effects and was satisfied with the treatment. Interestingly, she also reported improvement in respiratory symptoms. This may correlate with the proven efficacy of dual IL-4/IL-13 inhibitors in suppressing type 2 inflammation in AD and asthma, being the unique biologic monoclonal antibody approved for both conditions to date (5).

Figure 2. Response at six months after dupilumab.

It has been recognized that allergy and asthma often coexist with DAAT. Atopy, which predisposes to asthma, has also been reported to be more prevalent in patients with DAAT. Elevated release of inflammatory mediators due to the absence of AAT’s inhibitory function could result in persistent airway hyperreactivity and an asthmatic condition. Some authors say DAAT Pi*S and Pi*Z SERPINA1 variants are associated with asthma exacerbations. Our patient had the Pi*S Matawa genotype. However, the relationship between allergy, asthma, and AATD is still to be further characterized (7–10).

In patients who have both AD and concurrent asthma, blocking the IL-4 receptor effectively manages both conditions by inhibiting IL-4 and IL-13. Medications that exclusively target either IL-4 or IL-13 have not successfully treated asthma to date (5). This is another reason why dupilumab fit our patient’s profile best. Moreover, this could justify the improvement in the patient’s respiratory symptoms.

In conclusion, dupilumab has proven to be effective in the management of concurrent AD and asthma, underscoring the advantages for patients presenting both conditions, even in cases of latent tuberculosis infection. Moreover, the modulation of inflammatory pathways also helps mitigating the additional burden of potential respiratory conditions such as DAAT like in our patient.

Ethics statement

Ethics approval was not required for the treatment. Consent for publication of all patient photographs and medical information was provided.

Acknowledgments

The authors would like to thank Alvaro Prados-Carmona, MD, for his support in the writing of this manuscript. This research received no external funding.

Disclosure statement

The authors have no conflict of interest to declare.

Data availability statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Additional information

Funding

The author(s) reported there is no funding associated with the work featured in this article.