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Idiopathic, Refractory Sweet’s Syndrome Associated with Common Variable Immunodeficiency: a Case Report and Literature Review

  • Autoimmunity (T. Tarrant, Section Editor)
  • Published:
Current Allergy and Asthma Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Sweet’s syndrome (SS) is classically considered a hypersensitivity reaction often associated with autoimmune disorders and malignancy. SS has also been increasingly reported to occur with immunodeficiencies. We present a case of treatment-refractory, systemic SS as the initial manifestation in a young child with common variable immunodeficiency (CVID). We also review current literature about SS and concurrent immunodeficiencies and autoimmunity in CVID patients.

Recent Findings

Few case reports exist regarding the co-occurrence of Sweet’s syndrome and primary immunodeficiencies. SS is characterized by a pro-inflammatory state with a neutrophil predominance resulting in a spectrum of clinical manifestations. CVID is a multifactorial antibody deficiency that can be associated with autoimmunity, which some studies have proposed to be secondary to altered CD21 expression. SS occurring in patients with CVID has been infrequently reported, and one case study demonstrated improvement of Sweet’s associated skin lesions with immunoglobulin replacement. In our case, the patient had multi-system SS refractory to multiple immunomodulatory therapies. To our knowledge, this is the first report of the effective and safe use of intravenous tocilizumab and oral lenalidomide to treat SS in a child with CVID. Immunoglobulin replacement reduced the frequency of infections and may have contributed to the opportunity to wean the immunosuppressive therapies for Sweet’s syndrome.

Summary

Sweet’s syndrome as an initial manifestation of co-occurring immunodeficiencies is rare, and providers need a high index of suspicion. In addition, treatment of SS associated with an immunodeficiency can be a challenge. Treatment with immunoglobulin replacement reduces the frequency of infections, and in some patients with concurrent SS may improve skin lesions and reduce the need for immunomodulator therapy. Further study is necessary to better understand the pathogenesis of CVID in patients with SS and to identify possible biomarkers that predict who with SS are at risk for developing hypogammaglobulinemia.

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Abbreviations

AGEP:

Acute generalized exanthematic pustulosis

BAFF-R:

B cell activating factor receptor

CVID:

Common variable immunodeficiency

CGD:

Chronic granulomatous disease

G-CSF:

Granulocyte-colony stimulating factor

GLILD:

Granulomatous lymphocytic interstitial lung disease

HIV:

Human immunodeficiency virus

ICOS:

Inducible co-stimulator

RA:

Rheumatoid arthritis

SCID:

Severe combined immunodeficiency

SS:

Sweet’s syndrome

SLE:

Systemic lupus erythematosus

TACI:

Transmembrane activator calcium-modulator and cyclophilin ligand interactor

References

Papers of particular interest, published recently, have been highlighted as: •• Of major importance

  1. Abbott JK, Gelfand EW. Common variable immunodeficiency: diagnosis, management, and treatment. Immunol Allergy Clin N Am. 2015;35:637–58.

    Article  Google Scholar 

  2. Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015;136:1186–205e1-78.

    Article  Google Scholar 

  3. •• Marzano AV, Borghi A, Wallach D, Cugno M. A comprehensive review of neutrophilic diseases. Clin Rev Allergy Immunol. 2018;54:114–30. An in-depth comprehensive review article detailing pathogenesis, diagnosis, and management of neutrophilic dermatoses.

    Article  CAS  Google Scholar 

  4. Lipp K, Shenefelt P, Nelson R, Messina J, Fenske N. Persistent Sweet’s syndrome occurring in a child with a primary immunodeficiency. J Am Acad Dermatol. 1999;40:838–41.

    Article  CAS  Google Scholar 

  5. Gray PE, Bock V, Ziegler DS, Wargon O. Neonatal Sweet syndrome: a potential marker of serious systemic illness. Pediatrics. 2012;129:e1353–9.

    Article  Google Scholar 

  6. Lyon C, Griffiths C. Chronic granulomatous disease and acute neutrophilic dermatosis. Clin Exp Dermatol. 1999;24:368–71.

    Article  CAS  Google Scholar 

  7. Haliasos E, Soder B, Rubenstein D, Henderson W, Morrell D. Pediatric Sweet syndrome and immunodeficiency successfully treated with intravenous immunoglobulin. Pediatr Dermatol. 2005;22:530–5.

    Article  Google Scholar 

  8. Sillevis Smitt JH, Kuijpers TW. Cutaneous manifestations of primary immunodeficiency. Curr Opin Pediatr. 2013;25:492–7.

    Article  Google Scholar 

  9. Sedel D, Hueget P, Lebbe C, et al. Sweet syndrome as the presenting manifestation of chronic granulomatous disease in an infant. Pediatr Dermatol. 1994;11:237–40.

    Article  CAS  Google Scholar 

  10. Elliot S, Mallory S. Sweet syndrome: an unusual presentation of chronic granulomatous disease in a child. Infect Dis J. 1999;18:568–70.

    Article  Google Scholar 

  11. Knipstein J, Ambruso D. Sweet syndrome in an infant with chronic granulomatous disease. Pediatr Hematol Oncol. 2012;34:372–4.

    Article  Google Scholar 

  12. Cohen PR. Sweet's syndrome--a comprehensive review of an acute febrile neutrophilic dermatosis. Orphanet J Rare Dis. 2007;2:34.

    Article  Google Scholar 

  13. Anzalone CL, Cohen PR. Acute febrile neutrophilic dermatosis (Sweet’s syndrome). Curr Opin Hematol. 2013;20:26–35.

    Article  CAS  Google Scholar 

  14. Lipp K, Shenenfelt P, Nelson R, et al. Persistent Sweet's syndrome occurring in a child with a primary immunodeficiency. J Am Acad Dermatol. 1999;40:838–41.

    Article  CAS  Google Scholar 

  15. Boatman BW, Taylor RC, Klein LE, et al. Sweet’s syndrome in children. South Med J. 1994;87:193–6.

    Article  CAS  Google Scholar 

  16. Mohr MR, Torosky C, Hood AF, et al. Sweet syndrome in infancy. Pediatr Dermatol. 2010;27:208–9.

    Article  Google Scholar 

  17. Rochet NM, Chavan RN, Cappel MA, Wada DA, Gibson LE. Sweet syndrome: clinical presentation, associations, and response to treatment in 77 patients. J Am Acad Dermatol. 2013;69:557–64.

    Article  CAS  Google Scholar 

  18. Walker DC, Cohen PR. Trimethoprim-sulfamethoxazole-associated acute febrile neutrophilic dermatosis: case report and review of drug-induced Sweet's syndrome. J Am Acad Dermatol. 1996;34:918–23.

    Article  CAS  Google Scholar 

  19. Schadt CR, Callen JP. Management of neutrophilic dermatoses. Dermatol Ther. 2012;25:158–72.

    Article  Google Scholar 

  20. Garcovich S, De Simone C, Berti E, Marzano AV. Drug management of neutrophilic dermatoses. Expert Rev Clin Pharmacol. 2017;10:1119–28.

    Article  CAS  Google Scholar 

  21. Voelter-Mahlknecht S, Bauer J, Metzler G, Fierlbeck G, Rassner G. Bullous variant of Sweet's syndrome. Int J Dermatol. 2005;44:946–7.

    Article  Google Scholar 

  22. Marzano AV, Fanoni D, Antiga E, Quaglino P, Caproni M, Crosti C, et al. Expression of cytokines, chemokines and other effector molecules in two prototypic autoinflammatory skin diseases, pyoderma gangrenosum and Sweet's syndrome. Clin Exp Immunol. 2014;178:48–56.

    Article  CAS  Google Scholar 

  23. Marzano AV, Cugno M, Trevisan V, Lazzari R, Fanoni D, Berti E, et al. Inflammatory cells, cytokines and matrix metalloproteinases in amicrobial pustulosis of the folds and other neutrophilic dermatoses. Int J Immunopathol Pharmacol. 2011;24:451–60.

    Article  CAS  Google Scholar 

  24. Bourke JF, Jones JL, Graham-Brown RAC. An immunohistochemical study of the dermal infiltrate and epidermal staining for interleukin 1 in 12 cases of Sweet’s syndrome. Br J Dermatol. 1996;134:705–9.

    Article  CAS  Google Scholar 

  25. Kawakami T, Ohashi S, Kawa Y, Takahama H, Ito M, Soma Y, et al. Elevated serum granulocyte colony-stimulating factor levels in patients with active phase of sweet syndrome and patients with active Behcet disease: implication in neutrophil apoptosis dysfunction. Arch Dermatol. 2004;140:570–4.

    Article  CAS  Google Scholar 

  26. White JM, Mufti G, Salisbury JR, du Vivier AW. Cutaneous manifestations of granulocyte colony-stimulating factor. Clin Exp Dermatol. 2006;31:206–7.

    Article  CAS  Google Scholar 

  27. von den Driesch P. Sweet’s syndrome (acute febrile neutrophilic dermatosis). J Am Acad Dermatol. 1994;31:535–56.

    Article  Google Scholar 

  28. Omoya K, Naiki Y, Kato Z, Yoshioka S, Uchida Y, Taga T, et al. Sweet's syndrome in a neonate with non-B54 types of human leukocyte antigen. World J Pediatr. 2012;8:181–4.

    Article  Google Scholar 

  29. Tuerlinckx D, Bodart E, Despontin K, Boutsen Y, Godding V, Ninane J. Sweet’s syndrome with arthritis in an 8-month-old boy. J Rheumatol. 1999;26:440–2.

    CAS  PubMed  Google Scholar 

  30. Suehisa S, Tagami H, Inoue F, Matsumoto K, Yoshikuni K. Colchicine in the treatment of acute febrile neutrophilic dermatosis (Sweet's syndrome). Br J Dermatol. 1983;108:99–101.

    Article  CAS  Google Scholar 

  31. Horio T, Danno K, Okamoto H, Miyachi Y, Imamura S. Potassium iodide in erythema nodosum and other erythematous dermatoses. J Am Acad Dermatol. 1983;9:77–81.

    Article  CAS  Google Scholar 

  32. Horio T, Imamura S, Danno K, Furukawa F, Ofuji S. Treatment of acute febrile neutrophilic dermatosis (Sweet’s syndrome) with potassium iodide. Dermatologica. 1980;160:341–7.

    Article  CAS  Google Scholar 

  33. Berger TG, Dhar A, TH MC. Neutrophilic dermatoses in HIV infection. J Am Acad Dermatol. 1994;31:1045–7.

    Article  CAS  Google Scholar 

  34. Hilliquin P. Sweet’s syndrome and monoarthritis in a human immunodeficiency virus-positive patient. Arthritis Rheum. 1992;35:484–6.

    Article  CAS  Google Scholar 

  35. O'Regan GM, Ho WL, Limaye S, Keogan MT, Murphy GM. Sweet's syndrome in association with common variable immunodeficiency. Clin Exp Dermatol. 2009;34:192–4.

    Article  CAS  Google Scholar 

  36. Cunningham RC. The many faces of common variable immunodeficiency. Hematol Am Soc Hematol Educ Program. 2012;2012:301–5.

    Google Scholar 

  37. Gathmann B, Mahlaoui N, Ceredih, et al. Clinical picture and treatment of 2212 patients with common variable immunodeficiency. J Allergy Clin Immunol. 2014;134:116–26.

    Article  Google Scholar 

  38. Patuzzo G, Barbieri A, Tinazzi E, Veneri D, Argentino G, Moretta F, et al. Autoimmunity and infection in common variable immunodeficiency (CVID). Autoimmun Rev. 2016;15:877–82.

    Article  CAS  Google Scholar 

  39. Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C. Morbidity and mortality in common variable immune deficiency over 4 decades. Blood. 2012;119:1650–7.

    Article  CAS  Google Scholar 

  40. van Zelm MC. CD81 gene defect in humans disrupts CD19 complex formation and leads to antibody deficiency. J Clin Invest. 2010;120:1265–74.

    Article  Google Scholar 

  41. van Zelm MC, Reisli I, van der Burg M, et al. An antibody-deficiency syndrome due to mutations in the CD19 gene. N Engl J Med. 2006;354:1901–12.

    Article  Google Scholar 

  42. Thiel J, Kimmig L, Salzer U, Grudzien M, Lebrecht D, Hagena T, et al. Genetic CD21 deficiency is associated with hypogammaglobulinemia. J Allergy Clin Immunol. 2012;129:801–10.

    Article  CAS  Google Scholar 

  43. Kuijpers TW, Bende RJ, Baars PA, Grummels A, Derks IAM, Dolman KM, et al. CD20 deficiency in humans results in impaired T cell-independent antibody responses. J Clin Invest. 2010;120:214–22.

    Article  CAS  Google Scholar 

  44. Bossaller L, Burger J, Draeger R, Grimbacher B, Knoth R, Plebani A, et al. ICOS deficiency is associated with a severe reduction of CXCR5 + CD4 germinal center Th cells. J Immunol. 2006;177(7):4927–32.

    Article  CAS  Google Scholar 

  45. Zhang L, Radigan L, Salzer U, Behrens TW, Grimbacher B, Diaz G, et al. Transmembrane activator and calcium-modulating cyclophilin ligand interactor mutations in common variable immunodeficiency: clinical and immunologic outcomes in heterozygotes. J Allergy Clin Immunol. 2007;120:1178–85.

    Article  CAS  Google Scholar 

  46. Goldacker S, Warnatz K. Tackling the heterogeneity of CVID. Curr Opin Allergy Clin Immunol. 2005;5:504–9.

    Article  Google Scholar 

  47. Bacchelli C, Buckridge S, Thrasher AJ, Gaspar HB. Translational mini-review series on immunodeficiency: molecular defects in common variable immunodeficiency. Clin Exp Immunol. 2007;149:401–9.

    Article  CAS  Google Scholar 

  48. Cunningham-Rundles C, Radigan L. Deficient IL-12 and dendritic cell function in common variable immune deficiency. Clin Immunol. 2005;115:147–53.

    Article  CAS  Google Scholar 

  49. Azizi G, Abolhassani H, Asgardoon MH, Alinia T, Yazdani R, Mohammadi J, et al. Autoimmunity in common variable immunodeficiency: epidemiology, pathophysiology and management. Expert Rev Clin Immunol. 2017;13:101–15.

    Article  CAS  Google Scholar 

  50. Maglione PJ. Autoimmune and lymphoproliferative complications of common variable immunodeficiency. Curr Allergy Asthma Rep. 2016;16:19.

    Article  Google Scholar 

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Acknowledgments

We would like to express our gratitude to Dr. Michael Hershfield, Professor of Medicine and Biochemistry at Duke University for his assistance in evaluating our patient for ADA2 deficiency.

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Authors and Affiliations

  1. Division of Allergy, Immunology, and Rheumatology, Department of Pediatrics, University of North Carolina at Chapel Hill, 3300 Thurston Building, CB 7280, Chapel Hill, NC, 27599-7280, USA

    Quindelyn S. Cook & Eveline Y. Wu

  2. Department of Otolaryngology/Head and Neck Surgery, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Carlton J. Zdanski

  3. Department of Dermatology, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Craig N. Burkhart & Paul B. Googe

  4. Division of Pediatric Hematology-Oncology, Department of Pediatrics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA

    Patrick Thompson

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  1. Quindelyn S. Cook
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Correspondence to Quindelyn S. Cook.

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Drs. Cook, Googe, Wu, Zdanski, and Burkhart declare that they have no conflicts of interest.

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Cook, Q.S., Zdanski, C.J., Burkhart, C.N. et al. Idiopathic, Refractory Sweet’s Syndrome Associated with Common Variable Immunodeficiency: a Case Report and Literature Review. Curr Allergy Asthma Rep 19, 32 (2019). https://doi.org/10.1007/s11882-019-0864-4

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