Epidemiology and outcomes Lupus Sci Med: first published as 10.1136/lupus-2020-000411 on 22 September 2020. Downloaded from Cutaneous vasculitis in SLE Romy Kallas ,1 Daniel Goldman,2 Michelle A Petri 1 To cite: Kallas R, Goldman D, ABSTRACT prognosis.1–3 Among juvenile patients with Petri MA. Cutaneous vasculitis in Objectives We determined the temporal association SLE, those with acute cutaneous lupus erythe- SLE. Lupus Science & Medicine between clinical and serological disease manifestations matosus or non- scarring alopecia were more 2020;7:e000411. doi:10.1136/ and development of cutaneous small vessel vasculitis in a lupus-2020-000411 likely to develop arthralgia, while mucosal large prospective multiethnic cohort. ulcers were associated with a higher risk of Methods Patients with SLE diagnosed according to the leucopenia.1 In adult patients with SLE, the Systemic Lupus International Collaborating Clinics (SLICC) Received 24 April 2020 presence of malar rash was indicative of more Revised 17 August 2020 classification criteria or the revised classification criteria Accepted 24 August 2020 as defined by the American College of Rheumatology (ACR) severe systemic disease, while discoid lupus were enrolled in the Hopkins Lupus Cohort. Cutaneous appeared to be associated with a decreased 2 3 small vessel vasculitis was determined as a component of incidence of renal disease but an increased the Systemic Lupus Erythematosus Disease Activity Index. Systemic Lupus International Collaborating SLE- associated cutaneous small vessel vasculitis lesions Clinics/American College of Rheumatology were reported clinically. They presented as punctate Damage Index (SLICC/ACR DI).3 lesions, palpable purpura, tender erythematous plaques Cutaneous small vessel vasculitis is a non- or macules with or without necrosis. No histopathological specific cutaneous manifestation and is diagnosis was pursued to confirm the diagnosis of the most frequent type of vasculitis among vasculitis or to differentiate it from other causes of digital 4 5 lesions in patients with SLE. Disease manifestations patients with SLE. It is mostly skin limited that preceded the first occurrence of cutaneous small and is infrequently associated with systemic 5 6 4 5 7 vessel vasculitis lesions were analysed using Kaplan- vasculitis. It is seen in up to 20%. Cuta- Meier. Cox regression analysis was used to assess the neous small vessel vasculitis mostly pres- relationship between baseline clinical and immunological ents as punctate lesions, palpable purpura, manifestations and the development of cutaneous small ulcers, erythematous plaques or macules and vessel vasculitis. We adjusted for gender, race and age at erythema with necrosis that may occur once SLE diagnosis. or may be relapsing.5 Results A total of 2580 patients were studied: 52.4% were Caucasian and 39.4% were African- American. In the setting of Sjögren’s syndrome, devel- The mean age of the cohort was 45.5±14.5 years. The opment of cutaneous vasculitis signified more http://lupus.bmj.com/ mean years of cohort follow- up was 7.9±7.6. Cutaneous severe disease, including higher rates of joint small vessel vasculitis was observed in 449 (17.3%). The disease, peripheral neuropathy, renal involve- mean time to cutaneous vasculitis after SLE diagnosis ment, lymphoma, hospitalisation and even was 4.78 years (95% CI 3.96 to 5.60). At least 159 (35%) death.8 In the setting of rheumatoid arthritis, patients had recurrences of cutaneous vasculitis lesions. leucocytoclastic vasculitis had an unfavourable Discoid rash, Raynaud’s phenomenon, myositis, anaemia, prognosis with associations with mononeuritis Coombs’ positivity, leucopenia, anti- Smith and anti- RNP 9 multiplex and bowel involvement. on September 27, 2021 by guest. Protected copyright. (Ribonucleoprotein) were significantly associated with the development of cutaneous vasculitis. The SLICC/ACR In SLE, past studies evaluated the clinical Damage Index score was higher in patients with cutaneous and serological characteristics of patients vasculitis compared with those without cutaneous with combined cutaneous and visceral vascu- 4 5 10–12 vasculitis. litis. In these studies, SLE patients with © Author(s) (or their employer(s)) 2020. Re- use Conclusions Cutaneous vasculitis is frequent (17.3%) vasculitis were found to be mostly men, were 13 permitted under CC BY-NC. No and often recurrent (35%). African- Americans are at higher younger at SLE onset, had longer disease commercial re- use. See rights risk of developing cutaneous small vessel vasculitis than duration, livedo reticularis, haematolog- and permissions. Published by Caucasians. Clinical presentations such as myositis and ical parameters (anemia and high Erythro- BMJ. haematological manifestations are predictors of cutaneous 10 4 1 cyte Sedimentation Rate), anti- dsDNA, Division of Rheumatology, vasculitis development. The presence of cutaneous 11 5 12 Johns Hopkins Medicine, vasculitis is associated with increased organ damage. anti-SSA, anti- SSB and anti- Smith. Baltimore, Maryland, USA However, only 2% of patients with SLE have 2Department of Rheumatology, concomitant visceral and cutaneous vascu- Johns Hopkins University, litis.5 6 Moreover, as detailed in the Derma- Baltimore, Maryland, USA I- INTRODUCTION tologic Addendum to the 2012 Revised Correspondence to Lupus- specific cutaneous manifestations International Chapel Hill Consensus Confer- Dr Romy Kallas; kallasr@ mlhs. are important in relation to the develop- ence Nomenclature of Vasculitides, the org ment of systemic involvement and ultimate presentation of cutaneous vasculitis occurring Kallas R, et al. Lupus Science & Medicine 2020;7:e000411. doi:10.1136/lupus-2020-000411 1 Lupus Science & Medicine Lupus Sci Med: first published as 10.1136/lupus-2020-000411 on 22 September 2020. Downloaded from in patients with SLE is heterogeneous but is mostly small livedo and Raynaud’s phenomenon. The musculoskel- vessel vasculitis rather than medium vessel.14 Therefore, etal manifestations included arthralgias and arthritis. studies of cutaneous small vessel vasculitis are more rele- The renal data included proteinuria, haematuria, renal vant to clinical practice. insufficiency and renal failure. The neuropsychiatric One study of juvenile SLE patients with cutaneous manifestations included seizure, psychosis, meningitis, vasculitis alone found that it was associated with more stroke, lupus headaches, depression, mononeuritis seizures and granular casts.1 In adult patients with SLE, multiplex, cognitive impairment, optic neuritis, cranial having cutaneous vasculitis was associated with Raynaud’s neuropathy, peripheral neuropathy, longitudinal myelitis phenomenon,15 mucocutaneous and musculoskeletal or brain CT/MRI abnormalities. The haematological manifestations,7 myositis1 or no major organ involve- data included anaemia defined as haemoglobin less than ment.15 Cutaneous vasculitis was also found to correlate 11.0 g/dL in a woman and less than 12.0 g/dL in men, with disease activity1 5 7 16 and poor prognosis with renal haemolytic anaemia, leucopenia defined as white blood system and central nervous system (CNS) deterioration.16 cell count (WBC) <4000 documented two or more times Patients with cutaneous vasculitis were more likely to have when the patient was not on drugs known to cause bone antiribosomal P antibodies,15 anti- Ro antibody11 and cryo- marrow suppression and thrombocytopaenia defined as globulins.17 One study of patients with SLE reported an platelets <100 000, which was not due to medications. association with hypocomplementaemia and antiphos- Cardiac manifestations included myocarditis, Libman- pholipid syndrome.7 Sacks and cardiac murmur. Pulmonary manifestations The aim of this study was to determine the association included fibrosis and pulmonary hypertension. Gastroin- between clinical and serological manifestations of SLE testinal manifestations included hepatomegaly, increased and development of future cutaneous small vessel vascu- liver function tests, splenomegaly, gastrointestinal lupus litis, as well as the association between the presence of and pancreatitis. Sjögren’s syndrome was diagnosed cutaneous vasculitis and organ damage in a large prospec- in the presence of dry eyes confirmed by an abnormal tive multiethnic cohort. Schirmer test and/or low ocular surface staining not due to medications or dry eyes and dry mouth in the presence of anti- Ro and/or La antibodies. We also included venous PATIENTS AND METHODS and arterial thrombosis. The Hopkins Lupus Cohort is a longitudinal cohort The immunological data included anti-dsDNA, anti- of patients diagnosed with SLE at the Hopkins Lupus Smith, anti- RNP, anti- SSA, anti- SSB, lupus anticoagulant Center. All patients gave written informed consent to (by International Society on Thrombosis and Haemo- participate. Patients were followed up by protocol quar- stasis definitions), anticardiolipin IgG and IgM, anti- terly or more often as clinically indicated. A total of 2580 beta-2 glycoprotein IgG and IgM, C3 and C4 level and patients with SLE diagnosed according to the SLICC clas- CH50. 18 sification criteria or the revised classification criteria as The SLICC/ACR DI was used to measure damage, http://lupus.bmj.com/ defined by the ACR.19 20 defined as irreversible organ dysfunction, present for 6 months or longer, regardless of aetiology, in all organ Variables systems.21 The SLICC/ACR DI was calculated based on Cutaneous vasculitis was defined clinically by the presence