Urticarial vasculitis and asymptomatic acquired C1 esterase inhibitor deficiency revealing an angioimmunoblastic T cell lymphoma

ARTICLE

Auteur(s) : Clelia Moulin¹, Sébastien Debarbieux¹, Sophie Ducastelle-Lepretre², Nicole Fabien³, Lauriane Depaepe⁴, Cécile Veysseyre-Balter³, Véronique Fremeaux-Bacchi⁵, Sylvie Isaac⁴, Brigitte Balme⁶, Luc Thomas¹

¹Dermatology Department, HCL Lyon Sud 69495 Pierre Bénite, France
²Haematology Department, HCL Lyon Sud 69495 Pierre Bénite, France
³University of Lyon, Department of Immunology; INSERM U851; HCL Lyon-Sud, F-69495 Pierre-Benite, France
⁴Pathology department, HCL Lyon Sud, 69495 Pierre Bénite, France
⁵Biological Immunology Department, Hôpital Européen Georges Pompidou, Paris, France
⁶Dermatopathology Department, HCL Lyon Sud 69495 Pierre Bénite, France

A 60-year-old woman presented with a recurrent asymptomatic eruption of the legs that had lasted for 6 months. There was neither angioedema nor remarkable medical history. General examination revealed nothing more than a few urticarial papules on the inferior limbs. Histopathological examination of a skin biopsy showed lymphocytic and polymorphonuclear perivascular infiltrates without any alteration of vascular walls and no atypical cells. The clinical presentation and histopathological data, though not specific, were consistent with an urticarial vasculitis. Echocardiography, chest X-ray, and ultrasound scan of the abdomen and pelvis were normal. Full blood count and renal function were normal, ESR and serum C-reactive protein were low, serum lactate deshydrogenase and serum protein electrophoresis and immunofixation were normal (no hypergamma globulinemia (gamma globulins: 9.9 g/dL; normal range 8-13.5 g/dL) or monoclonal gammapathy). Prothrombin time was 100% and albuminemia was normal (45.5 g/dL). Anti-nuclear antibodies were positive (1600), with no specificity; anti-dsDNA antibodies were negative. Serologies of syphilis, hepatitis B, hepatitis C and HIV were negative. Beta2-microglobulinemia was slightly increased (3.3 mg/L); CH50, C4 and C1q levels were significantly decreased, whereas C3 was normal (CH50: 13.7 UH50/mL, normal range 42-61 UH50/mL; C4 < 0.045 g/L, normal range 0.1-0.4 g/L; C1q: 0.035 g/L, normal > 0.1 g/L); C1 esterase inhibitor (C1INH) level was decreased (C1INH activity: 0,12 (normal > 0,7) (chromogenic technic - Technochrom C1-Inh; Technoclone, Vienne, Autriche)); C1INH antigen: 0.09 (normal > 0.24 g/L) (radial immunodiffusion assay – NOR Partigen C1-Inhibitor Simens)); Anti-C1INH antibodies were negative (IgG, IgA and IgM < 10 UA/mL).

Such results were in favour of an acquired C1INH deficiency. The patient was therefore referred to haematologists. A TEP scan and surgical biopsy of a hypermetabolic inguinal adenopathy led to the diagnosis of an angio-immunoblastic T cell lymphoma (figure 1).

Acquired C1INH deficiency was classically considered to be related to activation of the classical pathway of the complement (type 1, mainly associated with B-cell lymphoproliferation) or neutralisation by antiC1INH autoantibodies (type 2, mainly associated with monoclonal gammapathy of undetermined significance (MGUS) and autoimmune conditions). It has now been shown that the reality is not so clear cut and the frequent coexistence of true B cell lymphoproliferations, non malignant B cell proliferations and autoimmune phenomenons has led to the current concept that increased C1INH consumption and C1INH neutralisation are frequently associated. Alterations in the control of B cell proliferation seems to be the common denominator [1, 2]. Since C1INH contributes to down-regulating bradykinin levels, its deficiency causes episodic angioedema, a rare clinical condition characterized by recurrent, localized, non-demarcated, non-pruritic subcutaneous swellings, which appear rapidly and resolve within hours to days. It can be potentially life threatening when affecting the upper-airways. Asymptomatic acquired C1INH deficiency is rare but has occasionally been found when systematically looked for in patients with lymphoproliferative disorders [3]; it has also been reported in association with autoimmune conditions [4]; thus it may be significantly underdiagnosed.

Angio-immunoblastic T-cell lymphoma (AITL) is a peripheral T-cell lymphoma, usually with a poor prognosis. The diagnosis requires a biopsy and histological examination of a pathologic lymph node (changes in peripheral blood and on bone marrow examination are usually non-specific). Various skin manifestations can be observed: transient morbilliform eruptions, infiltrated plaques, purpuric, urticarial or prurigolike lesions. Even when clinical and histological features are non-specific, skin lesions often seem to be clonally related to the nodal T-cell proliferation. Patients sometimes also have various symptomatic autoimmune manifestations [5].

The association of these 2 rare conditions, which has never been reported to our knowledge, seems more than fortuitous. It seems that LAI can be added to the list of malignancies that can potentially be associated with acquired C1INH deficiency.

Acknowledgements

References

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3 Bibi-Trikki T, Eclache V, Frilay Y, et al. Acquired C1 inhibitor deficiency associated with lymphoproliferative disorders: four cases. Rev Med Interne 2004; 25: 667-72.

4 Barilla-Labarca ML, Gioffrè D, Zanichelli A, Cicardi M, Atkinson JP. Acquired C1 esterase inhibitor deficiency in two patients presenting with a lupus-like syndrome and anticardiolipin antibodies. Arthritis Rheum 2002; 47: 223-6.

5 Dogan A, Attygalle AD, Kyriakou C. Angioimmunoblastic T-cell lymphoma. Br J Haematol 2003; 121: 681-91.