Received: 15 October 2017
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Accepted: 20 November 2017
DOI: 10.1111/dth.12582
THERAPEUTIC HOTLINE: LETTERS
Successful treatment of pyoderma gangrenosum with anakinra in a patient with Wiskott–Aldrich syndrome Dear Editor,
engagement, signaling events, and cytoskeletal rearrangement
Pyoderma gangrenosum (PG) is a rare, chronic, inflammatory disease,
(Buchbinder et al., 2014).
characterized by painful papules or pustules that rapidly evolve into
A 14-year-old Caucasian male presented to our Institute with a 5-
ulcers with irregular, undermined, and overhanging violaceous
month history of PG lesions (Figure 1a,b). His personal medical history
borders (Gameiro, Pereira, Cardoso, & Gonçalo, 2015). PG is more
was positive for WAS. Whole genome sequencing detected the muta-
frequent on lower extremities and in women between 20 and 50
tion inv(X)g.5721–11840, a rare inversion in WAS gene. In addition,
years of age (Gameiro et al., 2015). Up to 70% of PG patients show
the patient medical history was also positive for arthritis, Henoch–
an underlying systemic disease, including inflammatory bowel
€ nlein purpura, and a Crohn-like colitis, that led to subtotal colecScho
diseases, arthritis, and hematological malignancies (Gameiro et al.,
tomy and ileostomy. Several therapies were started to manage PG,
2015). Wiskott–Aldrich syndrome (WAS) is a rare X-linked primary
including systemic metil-prednisolone (5 mg/kg/day), minocycline
immunodeficiency
immunodeficiency,
(100 mg twice daily), cyclosporine (5 mg kg/day), and adalimumab
thrombocytopenia, and eczema (Buchbinder, Nugent, & Fillipovich,
(80 mg at week 0, 40 mg at week 1, followed by 40 mg every 15 days).
2014). The WAS gene (Xp11.22–p11.23) encodes the WAS protein,
However, no PG improvement was observed. Therefore, we decided to
involved in actin polymerization and associated coupling of receptor
start anakinra 100 mg once a day. Two months after a complete
characterized
by
severe
F I G U R E 1 (a) Right anterior elbow with typical features of PG; (b) Left anterior elbow with typical features of PG; (c) Right anterior elbow. Resolution of PG after a treatment with anakinra; (d) Resolution of the left anterior elbow PG
Dermatologic Therapy. 2017;e12582. https://doi.org/10.1111/dth.12582
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healing was shown. After a follow-up of 12 months (Figure 1c,d) the
ORC ID
patient did not show any recurrence.
Giovanni Paolino
PG is an uncommon ulcerative skin disorder that occurs in all age
Dario Didona
ET AL.
http://orcid.org/0000-0002-4146-8975 http://orcid.org/0000-0002-6119-1870
group. Approximately, 4% of patients are infants and children (Gameiro et al., 2015). Several differences have been reported between child-
Santo Raffaele Mercuri1, Giovanni Paolino1,2
hood and adult PG features. Indeed, in pediatric patients PG involve mainly head and ano-genital region, and it is mostly associated with
Eduardo De Flammineis1, Dario Didona3 1
Unit of Dermatology and Cosmetology, IRCCS University Vita-Salute San
ulcerative colitis, leukemia, and immunodeficiency (Hausmann & Dedeoglu, 2013). WAS is a primitive immunodeficiency characterized by thrombocytopenia, and eczema (Buchbinder et al., 2014). In addi-
,
, Pina Brianti1
Raffaele, Milan, Italy 2
Department of Dermatology, La Sapienza University of Rome, Italy 3
First Division of Dermatology, IRCCS Istituto Dermopatico
tion, WAS has been described in association with hemolytic anemia,
dell’Immacolata, Rome, Italy
vasculitis, renal disease, chronic arthritis, vasculitis, inflammatory bowel disease, and lymphomas (Buchbinder et al., 2014). Lack of WAS protein, due to WAS gene mutation, lead to cytoskeletal defects. The consequent immunodeficiency involves mainly T cells and is associated with both quantitative and qualitative defects in T cells (Rivers &
Correspondence Dario Didona, Prima Divisione Dermatologica, Istituto Dermopatico dell’Immacolata-IRCCS, via dei Monti di Creta 104, 00167 Roma, Italia. Email:
[email protected]
Thrasher, 2017). Although the pathogenesis of PG is not well understood, in our patient the cytoskeletal defects might have induced the
R EFE R ENC E S
initial formation of ulcerative lesions. Anakinra is a recombinant circu-
Beynon, C., Chin, M. F., Hunasehally, P., Bhagwandas, K., Bevan, M., Taylor, M., & Lawson, T. (2017). Successful treatment of autoimmune disease-associated pyoderma gangrenosum with the IL-1 receptor antagonist anakinra: A case series of 3 patients. Journal of Clinical Rheumatology, 23(3), 181–183.
lating IL-1 receptor antagonist which has been successfully used to treat auto-inflammatory diseases, which are characterized by aberrant activation of the IL-1 pathway (Beynon et al., 2017). In our case, the additional immunosuppressive effect of anti-IL-1 treatment in an immunodeficient patient could have increase the risk of complications. However, the experience of Mulders-Manders, Baas, Molenaar, and Simon (2017), who performed renal transplantation in three patients continuing therapy with anakinra before, during, and after the transplantation, led us to treat our patient with anakinra. This report highlights that the use of anakinra is effective in treating PG. In addition, our experience demonstrates that anakinra is safe also in immunodeficient patients. Finally, the response of PG to anakinra may highlight that IL-1 may play a pivotal role in PG pathogenesis.
CONFLIC T OF I NTE R ES T The authors declare no conflict of interest.
Buchbinder, D., Nugent, D. J., & Fillipovich, A. H. (2014). Wiskott-Aldrich syndrome: Diagnosis, current management, and emerging treatments. The Application of Clinical Genetics, 7, 55–66. Gameiro, A., Pereira, N., Cardoso, J. C., & Gonçalo, M. (2015). Pyoderma gangrenosum: Challenges and solutions. Clinical, Cosmetic and Investigational Dermatology, 8, 285–293. Hausmann, J. S., & Dedeoglu, F. (2013). Autoinflammatory diseases in pediatrics. Dermatologic Clinics, 31(3), 481–494. Mulders-Manders, C. M., Baas, M. C., Molenaar, F. M., & Simon, A. (2017). Peri- and postoperative treatment with the interleukin-1 receptor antagonist anakinra is safe in patients undergoing renal transplantation: Case series and review of the literature. Frontiers in Pharmacology, 8, 342. Rivers, E., & Thrasher, A. J. (2017). The Wiskott-Aldrich syndrome: Wiskott-Aldrich syndrome protein: Emerging mechanisms in immunity. European Journal of Immunology, 47, 1857–1866.
