**2. A rheum with a different view**

In this section, lupus will be discussed pragmatically. Most practitioners are unaccustomed to viewing disease features from a rheumatologic standpoint. Typically, the practitioner that approaches a patient with a plethora of symptoms, would order blood tests, and conclude a diagnosis of lupus; however, in this part of the chapter, we will discuss the need to focus "outside the box" and perhaps consider lupus as simply one of various other scenarios.

#### **2.1 Finding evidence of lupus**

Features of lupus considered in the differential diagnoses of other conditions include rashes, arthritis, renal disease (glomerular or tubular), Raynaud's phenomenon, sicca syndrome and muscle weakness. The differential diagnoses for these features often include lymphoma, sarcoidosis, phospholipid antibody syndrome, rheumatoid arthritis, inflammatory myopathy, Sjogren's syndrome, IgG4-related disease and scleroderma.

A lupus rash, seen with or without vasculitis, typically small vessel-showing leukocytoclastic vasculitis, is seen at the dermal/epidermal junction with immunofluorescence positive for IgG and complements [5]. Small vessel vasculitis is responsible for much of the severe abdominal pain seen in lupus patients.

Arthritis of lupus is inflammatory but not erosive. Differential diagnoses would include rheumatoid arthritis, gout, or psoriatic arthritis. Rheumatoid arthritis, psoriatic arthritis, scleroderma, sarcoid and gout are all destructive arthritic diseases [6].

Renal pathology is often noted due to blood or protein in the urine. It may be diagnosed by a decrease in renal function, which is differentiated on biopsy. Lupus tends to involve glomerulus with a "full house" pattern on immunofluorescent staining (i.e., presence of glomerular deposits that stain for IgG, IgM, IgA, C3 and C1q). This is the only organ finding to satisfy the SLICC criteria on its own in patients with systemic lupus. IgG and complements would be suggestive of lupus nephritis in a patient with proliferative glomerulonephritis. This may be focal, diffuse or pure membranous nephropathy [7]. A patient with pure membranous disease, high double stranded DNA and low complements often do not apply. Proliferative lesions are often seen in the face of rising double stranded DNA and consumption of complement levels. These levels are not subject to change in Sjogren's, scleroderma, sarcoid, or IgG4-related disease. (IgG4-related disease is unique, as both tubulointerstitial diseases occur simultaneously with glomerular disease). ANCA vasculitis shows pauci-immune deposits [8], while sarcoidosis would show granulomas without positive stain for immunofluorescence. Goodpasture syndrome will show anti-GBM antibodies [9]. Sjogren's syndrome will show renal tubular acidosis, and only rarely, glomerular disease [10]. Most cases of tubulointerstitial nephritis are drug-induced, and may be caused by medications, such as antibiotics medications, NSAIDs, proton pump inhibitors,

**5**

related disease, or sarcoid.

*Don't Miss Lupus*

*DOI: http://dx.doi.org/10.5772/intechopen.96892*

features of the disease [16].

hepatitis C infection [18].

systemic lupus, myopathy and vasculitis [21].

and immune-checkpoint inhibitors [11]. Uncommonly, NSAIDs may cause a combination of interstitial nephritis and nephrotic syndrome. Infections (i.e., legionella or *Mycobacterium tuberculosis* infection), may lead to a diagnosis of tubulointerstitial nephritis; however, autoimmune diseases, such as systemic lupus, sarcoidosis, Sjogren's syndrome, and uveitis syndrome, are also proven to cause tubulointerstitial nephritis [12]. Approximately 10–20% of patients diagnosed with lupus nephritis, have isolated lupus membranous nephropathy (class V), with no associated proliferative lesion present [13]. In patients with lupus nephritis, tubulointerstitial interstitial nephritis may accompany glomerular lesions, which is a risk factor for a poor outlook [14]. The IgG4 is a diagnostic differential and reveals tubulointerstitial nephritis, repeatedly associated with hypocomplementemia and hypodense nodular lesions, which can be seen on contrast-enhanced computerized tomography [15]. Tissue eosinophilia and deposits in the tubular basement membrane are often present, in addition to the distinctive pathological

Pulmonary renal syndromes can be seen in a very similar fashion, adding that lupus may present with acute glomerulonephritis, proliferative in nature, in addition to concurrent alveolar hemorrhage or diffuse interstitial infiltrates [17]. This pattern of disease seen in ANCA vasculitis is predominantly granulomatous polyangiitis, microscopic polyangiitis, and cryoglobulinemia, which is associated with

Oral and ocular dryness, with or without uveitis, are features of lupus [19]. Uveitis is frequently seen in sarcoidosis and described in IgG4-related disease and HLA-B27-related conditions, while corneal-related disease has a differential diagnosis in rheumatoid arthritis, myopathy, and phospholipid antibody syndrome.

Primary muscle weakness while in lupus, [20] is part of a differential diagnoses that includes polymyositis, dermatomyositis, immune mediated necrotizing myopathy, lupus with myopathy, sarcoidosis with myopathy and Crohn's with myopathy. The latter two, show non-caseating granuloma disease on biopsy, while lupus shows diffuse immunofluorescence, mainly immunoglobulins and complements. This could be referred to as a "recurring theme" in lupus deposits of immunoglobulin and complements. Cocaine-laced with levamisole is in the differential diagnosis

A rheumatologist should recognize a lupus patient by the malar rash sparing the nasolabial folds, "classic kidney biopsy" and other constellations, such as "non-scarring alopecia" and "discoid lupus". These cases are often straightforward, and do not require biopsy. The classic malar rash sparing the nasolabial folds, is a known hallmark of lupus; although it may be confused with rosacea or polymorphous light eruption. The malar rash with autoantibodies, particularly ANA (almost 100% sensitive), and anti-double stranded DNA (95% specific), will lend themselves to a conclusive diagnosis [22]. Nonetheless, it should be noted that research criteria is not necessary for a diagnosis of lupus. The research criterion is merely a tool, used to randomize patients into homogeneous groups, while in fact physicians are treating a heterogeneous disease. So, in the quest to stratify patients by nonskilled physicians, or those not comfortable diagnosing or treating lupus properly, diagnostic criteria is often helpful, but certainly cannot be the quintessential element of a lupus diagnosis. In reality, actually "labeling" a patient with a lupus diagnosis may require a protracted course. Theoretically, a patient may carry a label of unspecified connective tissue disease (UCTD) for some time, before a conclusive diagnosis can be given. In time, this patient may develop lupus, Sjogren's syndrome, rheumatoid arthritis, scleroderma, myositis, an overlap syndrome, anti-synthetase syndrome, Sjogren's syndrome, IgG4-

#### *Don't Miss Lupus DOI: http://dx.doi.org/10.5772/intechopen.96892*

and immune-checkpoint inhibitors [11]. Uncommonly, NSAIDs may cause a combination of interstitial nephritis and nephrotic syndrome. Infections (i.e., legionella or *Mycobacterium tuberculosis* infection), may lead to a diagnosis of tubulointerstitial nephritis; however, autoimmune diseases, such as systemic lupus, sarcoidosis, Sjogren's syndrome, and uveitis syndrome, are also proven to cause tubulointerstitial nephritis [12]. Approximately 10–20% of patients diagnosed with lupus nephritis, have isolated lupus membranous nephropathy (class V), with no associated proliferative lesion present [13]. In patients with lupus nephritis, tubulointerstitial interstitial nephritis may accompany glomerular lesions, which is a risk factor for a poor outlook [14]. The IgG4 is a diagnostic differential and reveals tubulointerstitial nephritis, repeatedly associated with hypocomplementemia and hypodense nodular lesions, which can be seen on contrast-enhanced computerized tomography [15]. Tissue eosinophilia and deposits in the tubular basement membrane are often present, in addition to the distinctive pathological features of the disease [16].

Pulmonary renal syndromes can be seen in a very similar fashion, adding that lupus may present with acute glomerulonephritis, proliferative in nature, in addition to concurrent alveolar hemorrhage or diffuse interstitial infiltrates [17]. This pattern of disease seen in ANCA vasculitis is predominantly granulomatous polyangiitis, microscopic polyangiitis, and cryoglobulinemia, which is associated with hepatitis C infection [18].

Oral and ocular dryness, with or without uveitis, are features of lupus [19]. Uveitis is frequently seen in sarcoidosis and described in IgG4-related disease and HLA-B27-related conditions, while corneal-related disease has a differential diagnosis in rheumatoid arthritis, myopathy, and phospholipid antibody syndrome.

Primary muscle weakness while in lupus, [20] is part of a differential diagnoses that includes polymyositis, dermatomyositis, immune mediated necrotizing myopathy, lupus with myopathy, sarcoidosis with myopathy and Crohn's with myopathy. The latter two, show non-caseating granuloma disease on biopsy, while lupus shows diffuse immunofluorescence, mainly immunoglobulins and complements. This could be referred to as a "recurring theme" in lupus deposits of immunoglobulin and complements. Cocaine-laced with levamisole is in the differential diagnosis systemic lupus, myopathy and vasculitis [21].

A rheumatologist should recognize a lupus patient by the malar rash sparing the nasolabial folds, "classic kidney biopsy" and other constellations, such as "non-scarring alopecia" and "discoid lupus". These cases are often straightforward, and do not require biopsy. The classic malar rash sparing the nasolabial folds, is a known hallmark of lupus; although it may be confused with rosacea or polymorphous light eruption. The malar rash with autoantibodies, particularly ANA (almost 100% sensitive), and anti-double stranded DNA (95% specific), will lend themselves to a conclusive diagnosis [22]. Nonetheless, it should be noted that research criteria is not necessary for a diagnosis of lupus. The research criterion is merely a tool, used to randomize patients into homogeneous groups, while in fact physicians are treating a heterogeneous disease. So, in the quest to stratify patients by nonskilled physicians, or those not comfortable diagnosing or treating lupus properly, diagnostic criteria is often helpful, but certainly cannot be the quintessential element of a lupus diagnosis. In reality, actually "labeling" a patient with a lupus diagnosis may require a protracted course. Theoretically, a patient may carry a label of unspecified connective tissue disease (UCTD) for some time, before a conclusive diagnosis can be given. In time, this patient may develop lupus, Sjogren's syndrome, rheumatoid arthritis, scleroderma, myositis, an overlap syndrome, anti-synthetase syndrome, Sjogren's syndrome, IgG4 related disease, or sarcoid.
