Case Letter

Antineutrophil Cytoplasmic Antibody Vasculitis Induced by Hydralazine

Cutis. 2020 January;105(01):E32-E35

References

Yokogawa N, Vivino FB. Hydralazine-induced autoimmune disease: comparison to idiopathic lupus and ANCA-positive vasculitis. Mod Rheumatol. 2009;19:338-347.
Agarwal G, Sultan G, Werner SL, et al. Hydralazine induces myeloperoxidase and proteinase 3 anti-neutrophil cytoplasmic antibody vasculitis and leads to pulmonary renal syndrome. Case Rep Nephrol. 2014;2014:868590.
Keasberry J, Frazier J, Isbel NM, et al. Hydralazine-induced anti-neutrophilic cytoplasmic antibody-positive renal vasculitis presenting with a vasculitic syndrome, acute nephritis and a puzzling skin rash: a case report. J Med Case Rep. 2013;7:20.
ten Holder SM, Joy MS, Falk RJ. Cutaneous and systemic manifestations of drug-induced vasculitis. Ann Pharmacother. 2002;36:130-147.
Namas R, Rubin B, Adwar W, et al. A challenging twist in pulmonary renal syndrome. Case Rep Rheumatol. 2014;2014:516362.
Dobre M, Wish J, Negrea L. Hydralazine-induced ANCA-positive pauci-immune glomerulonephritis. Ren Fail. 2009;31:745-748.
Hogan JJ, Markowitz GS, Radhakrishnan J. Drug-induced glomerular disease: immune-mediated injury. Clin J Am Soc Nephrol. 2015;10:1300-1310.
Radic M, Martinovic Kaliterna D, Radic J. Drug-induced vasculitis: a clinical and pathological review. Neth J Med. 2012;70:12-17.
Babar F, Posner JN, Obah EA. Hydralazine-induced pauci-immune glomerulonephritis: intriguing case series misleading diagnoses. J Community Hosp Intern Med Perspect. 2016;6:30632.
Marina VP, Malhotra D, Kaw D. Hydralazine-induced ANCA vasculitis with pulmonary renal syndrome: a rare clinical presentation. Int Urol Nephrol. 2012;44:1907-1909.
Magro CM. Associated ANCA positive vasculitis. The Dermatologist. 2015;23(7). http://www.the-dermatologist.com/content/associated-anca-positive-vasculitis. Accessed January 30, 2020.
Gao Y, Zhao MH. Review article: Drug-induced anti-neutrophil cytoplasmic antibody-associated vasculitis. Nephrology (Carlton). 2009;14:33-41.
Grau RG. Drug-induced vasculitis: new insights and a changing lineup of suspects. Curr Rheumatol Rep. 2015;17:71.
Sangala N, Lee RW, Horsfield C, et al. Combined ANCA-associated vasculitis and lupus syndrome following prolonged use of hydralazine: a timely reminder of an old foe. Int Urol Nephrol. 2010;42:503-506.
Choi HK, Merkel PA, Walker AM, et al. Drug-associated antineutrophil cytoplasmic antibody-positive vasculitis: prevalence among patients with high titers of antimyeloperoxidase antibodies. Arthritis Rheum. 2000;43:405-413.
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A comprehensive drug history from at least 6 months prior to presentation is essential. Biopsies also are strongly encouraged to confirm the presence of vasculitis and to determine its severity.^8,12 If renal biopsies are performed, they typically show scant IgG, IgM, and C3 deposition that is characteristic of ANCA-positive pauci-immune glomerulonephritis. Compared to hydralazine-induced lupus, renal involvement in the setting of HIAV has a relative lack of immunoglobulin and complement deposition with histopathology and immunostaining.¹⁴

Laboratory test results including serum MPO-ANCA (perinuclear ANCA) with coexisting elastase and/or lactoferrin autoantibodies is characteristic of HIAV. Antinuclear antibody, antihistone, anti–double-stranded DNA, and antiphospholipid antibodies along with low complement levels also may be present.^{2,4,9,10,13,15} It is recommended that ANCA assays combine indirect immunofluorescence with antigen-specific enzyme-linked immunosorbent assay.⁸ With respect to its idiopathic counterpart, patients may only present with MPO-ANCA, while other aforementioned antibodies (eg, antihistone, anti–double-stranded DNA) are rarely found or are entirely absent.^2,9 Patients with HIAV often have higher titers of MPO-ANCA.^9,15 In hydralazine-induced lupus, patients rarely have MPO-ANCA.

When a diagnosis of HIAV is made, it cannot be confirmed until hydralazine is discontinued and the patient’s symptoms resolve. Therefore, it is both diagnostic and therapeutic to discontinue hydralazine when HIAV is suspected. If recognized when the patient is only presenting with nonspecific symptoms, simple hydralazine cessation may be all that is needed; however, because recognition and diagnosis of HIAV is difficult, most patients present when the disease is severe and has progressed to organ involvement.^8-10

Treatment recommendations are highlighted in Table 2.^8,9,12 Glucocorticoid therapy is believed to work by preventing T-cell and B-cell maturation needed to produce MPO-ANCA. Rituximab, on the other hand, is suspected to act by clearing the peripheral blood of MPO-ANCA B cells.^12,16 Of note, patients with HIAV are different from their idiopathic counterparts because they usually need shorter courses of immunosuppressive therapy, long-term maintenance usually is unnecessary, and their prognosis generally is good if the offending agent is withdrawn.^7-9,12 Once the appropriate therapy is instituted, vasculitic manifestations are expected to resolve 10 days to 8 months after hydralazine cessation; however, a response often is seen within 1 to 4 weeks after initiation of systemic treatment.^4,8 Serum ANCA should be monitored, and there should be surveillance for the emergence of a chronic underlying vasculitis.^8,12

Our patient highlights the importance of identifying individuals at risk for HIAV. We seek to increase recognition of this entity, as it is not commonly seen in a dermatologic setting and is associated with high morbidity and mortality, as seen in our patient.

Antineutrophil Cytoplasmic Antibody Vasculitis Induced by Hydralazine

References

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