2023 Rheumatology at BMJ

Review

Table 1 Organ involvement in IgA vasculitis, systemic lupus erythematosus, cryoglobulinaemic disease, anti-GBM disease and ANCA-associated vasculitis. In general, frequencies of reported organ involvement depend on recruiting physician profession (rheumatologist, nephrologist, ENT surgeon and so on) and age of the patients (ie, kidney disease in younger IgA vasculitis less frequent than in adults, and vice versa in SLE).

Cryoglobulinaemic disease 77

ANCA-associated vasculitis 50

IgA vasculitis 72 (%)

Type 1 Cryo (%)

HCV-related life-threatening Cryo (%)

Anti-GBM disease 19 (%)

HCV-related mixed Cryo (%)

Non-infectious mixed Cryo (%)

SLE 73–76 (%)

GPA (%)

MPA (%) EGPA (%)

Kidney

38.8

49 33 83

73 18 66

58.6 63.1 34.7 82.3 31.2 18.7

82.2 62.8 29.5 25.8 36.6 22.2

26.4 88.7 47.2 70.6 66.2 29.9

Lung Skin

–

30–60

100

– – – –

ENT

– –

42.9*

–

Neurology

45 16

Gastrointestinal

27.1

8–10

*Nasal symptoms only, but a particular focus on nasal investigation. ANCA, anti-neutrophil cytoplasm-antibody; Cryo, cryoglobulinaemia; EGPA, eosinophilic granulomatosis with polyangiitis; ENT, ear, nose and throat; GBM, glomerular basement membrane; GPA, granulomatosis with polyangiitis; HCV, hepatitis C virus; MPA, microscopic polyangiitis; SLE, systemic lupus erythematosus.

Presenting symptoms together with pathogenetic insights of the five diseases which we focus on in this review are summarised below. IgA vasculitis IgAV is more common in childhood and presents less frequently with kidney involvement in comparison to adulthood. 4 The presence of a skin rash is a prerequisite of the disease, and often self-limiting. 5 Renal involvement is considered an entity with IgA-dominant glomerulonephritis, very much similar to the more frequently occurring IgA nephropathy (IgAN). In the skin, IgA deposits typically occur in foci with small vessel vascu- litis. In particular in children, the presenting symptoms of skin involvement on the legs are most commonly known as Henoch- Schönlein purpura, but there are many manifestations for which the term IgA vasculitis is used that are less well defined. Clinical symptoms indicative of renal involvement may not always lead to performance of a renal biopsy—but if they do, the findings in the biopsy may be similar in various aspects to IgAN: both enti- ties share the presence of IgA1 subclass in circulating immune complexes resulting in a pattern of IgA deposition in mesangial areas (figure 1A), accompanied by characteristic mesangial hypercellularity by light microscopy (figure 2A). 6 In combination with IgA1 deposition, complement C3 is frequently detected in glomeruli, reflecting the involvement of the lectin and alterna- tive pathway in IgAV pathogenesis. 5 It is generally considered

that endocapillary hypercellularity and crescent formation are more commo than its counterpart IgAN, perhaps in relation to the occurrence of deposits along capillary loops in addition to those in mesangial areas. In IgAN, extracapillary proliferation is regarded as an independent variable associated with a faster decline of kidney function. 7 LN in systemic lupus erythematosus LN will ultimately be present in at least 50% of systemic lupus erythematosus (SLE) cases, and proteinuria, in some subjects presenting with severe nephrosis (including respiratory compro- mise, pitting oedema, severe hypertension), is the presenting feature in most patients. In the absence of other pathologies, LN classes III, IV and V require immunosuppressive therapy. 8 LN is characterised by the most extensive pattern of deposition known in renal histology where all a so-called full house staining pattern (referring to simultaneous positivity for IgA, IgG, IgM, C3, C1q and light chains, depicted in figure 3A–G) in glomeruli present in various deposition patterns (mesangial (figure 2B), endocapillary (figure 2D) and membranous) are encountered, which together, form the basis for the distinction in LN classes, and moreover, they are closely associated with clinical symptoms (figure 4). 9 A multitude of antibodies and immune complexes are involved in LN, and although the inflammatory process may be destroying the glomerular structure, the deposits that have trig- gered this process in the first place, remain visible in the midst

Table 2 Differences between nephritic and nephrotic diseases. Variations in presentation need to be expected in patients presenting with the underlying diseases. This refers to the ‘standard’ presentation of a patient, but note that there are exceptional cases (ie, patients with severe lupus nephritis and acute kidney failure). Nephritic syndrome Nephrotic syndrome Onset Mainly abrupt Insidious-abrupt Kidney function Variable, from no/slow progression (many cases with IgA nephropathy) to RPGN Mainly no significant kidney function impairment at baseline Proteinuria Variable, absent in some patients ‘Nephrotic-range’ (>3–3.5 g/day, depending on definitions) proteinuria seen in most cases Haematuria Feature of ‘nephritis’; gross haematuria (visible blood) only in a minority of cases Variable, absent in most patients Blood pressure Raised (most cases), patients often remain hypertensive (even after achieving remission) Normal/raised (hypertensive often because of fluid overload) Serum albumin Normal/low Low (in ‘idiopathic’ cases), <2.5 g/dL Hypercoagulability Present in some forms (ie, AAV) Present in nephrotic stages (up to 40% with thrombosis) Lipid levels No change/reduced during active stages Hyperlipidaemia AAV, ANCA-associated vasculitis; RPGN, rapidly progressive glomerulonephritis.

Kronbichler A, et al . Ann Rheum Dis 2023; 82 :585–593. doi:10.1136/annrheumdis-2022-222495

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