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Small Animal Rehabilitation Centre 01225 982777

It’s Lupus, just like in House!

History

A 9 year old, female (neutered) Labrador presented to the medical referral team for investigation into urinary incontinence and occasionally passing large urinations overnight. DHPL4 was up to date and the last parasite treatment was given 3 months prior. Recent bloods showed mild hypoalbuminaemia (22.5g/L; Ref. 26.3-38.2) with concurrent hyperglobulinaemia (54.5g/L; Ref. 23-42) and mild ALP elevation (3xURL). T4 was 12.2 and the urine had a USG of 1.047 with 2+ bilirubin and 3+ protein. Three years prior to this presentation, at a different practice, there was a suspicion of Lyme disease based on lameness and pyrexia following a tick removal. This was never confirmed but treated using doxycycline. There was an apparent reaction to doxycycline leading to skin lesions and facial oedema and ultimately steroids were used to dampen down the presumed allergic reaction. In the recent consult the owner reported there was PU/PD (despite the normal USG). There were no additional findings on clinical exam, except a borderline pyrexia of 39.1C.

Initial problem list and differentials:

1. Incontinence - Genuine Incontinence

                            -> urinary incontinence = poor bladder storage function, anatomic, BSMI

                            -> overflow caused by urine retention = structural vs functional

                            - Secondary to/exacerbated by PU/PD

2. Overnight urination – Behavioural; Incontinence differentials as above

3. Hypoalbuminaemia with hyperglobulinaemia – PLN; acute phase response; lymphoproliferative disorders (lymphoma, multiple myeloma, leukemia); infectious causes; hepatic disease          

4. ?PU/PD? – Most commonly renal disease, diabetes mellitus/insipidus, HAC, endotoxaemia, hypercalcaemia, neoplasia.

5. ?Significant proteinuria? – Glomerulonephritis, urinary tract infection, HAC, lymphoproliferative disorders  other neoplastic, amyloidosis.

6. ?Significant bilirubinuria? – Intravascular haemolysis, hepatic disease, post-hepatic disease, normal some dogs.

[Mildly low T4 (sick euthyroid vs hypothyroid), borderline pyrexia and mild ALP elevations – considered non-specific and not useful to consider differentials at this stage.]

Initial Investigations and results

Initial investigations began with repeating a general blood profile. This showed the albumin had returned to normal (29), the globin remained elevated at 58 and there was now a mild anaemia (PCV 34%) and thrombocytopaenia (75). Abdominal ultrasound revealed a large heterogenous spleen of which FNAs were taken following normal PT/APTT values. Urinalysis was requested to quantify the proteinuria along with a BAST to assess hepatic function.

Splenic FNAs showed extramedullary haematopoiesis with lymphoid hyperplasia which may be observed with a variety of infectious diseases (including Ehrlichia and Leishmania) as well as immune-mediated disease. Early myeloma could not be excluded.

Urinalysis showed a UPC of 3.34 with no culture. BAST was considered normal.

Updated problem list

Incontinence/overnight urination/PUPD as before.

Splenomegaly with EMH and lymphoid hyperplasia – Consider immune mediated disease, early myeloma or infectious diseases.

Improved hypoalbuminaemia with hyperglobulinaemia.

Proteinuria with a UPC of 3.34 – UPCs greater than 2 are suggestive of glomerular disease (primary or secondary).

Further investigations

Based on the results we wanted to further exclude lymphoproliferative diseases. We requested serum protein electrophoresis which confirmed a polyclonal gammopathy. A travel screen was requested despite no history of travel, as this included a Borrelia PCR. This returned negative PCRs for Borrelia, Ehrlichia, Dirofilaria and Anaplasma. Ruling out these causes left us with immune mediated disease as the most likely candidate. A slide agglutination test was performed (figure 1) which was positive and an anti-nuclear antibody (ANA) serology test requested which was positive @1:128.

Diagnosis

Systemic Lupus Erythematosus (SLE) - diagnosis based on the persistent proteinuria (glomerular disease), concurrent IMHA/thrombocytopaenia (Evan’s syndrome) and positive ANA serology.

Treatment

The use of Prednisolone was debated given the proteinuria, however ultimately prednisolone was begun at 1mg/kg BID alongside Benazepril and Clopidogrel. Re-evaluation just over a week into treatment showed marked improvements in platelet numbers (manual count at least 150 minimum), PCV and no slide agglutination (figure 1). UPC had dropped to 0.5. The benazepril and clopidogrel were stopped after 2 weeks and the prednisolone tapered slowly over the following months. Whilst on the prednisolone the incontinence initially worsened and phenylpropanolamine was used try and control this. The UPC increased following benazepril cessation and so benazepril was re-introduced for the remainder of the steroid course. As the prednisolone was tapered the incontinence improved without the need for long term medications.

 

Figure 1. Slide agglutination tests pre-treatment (left) and 1 week after glucocorticoids (right). Note the strong positive agglutination prior to treatment.

Discussion

A diagnosis of SLE is considered if an animal displays 3 or more of the proposed criteria in Table 1.

ANA positive titre without another cause
Cutaneous Lesions – biopsy findings consistent with SLE
Persistent proteinuria or glomerulonephritis (with no other cause)
Non-erosive non-septic polyarthritis
Polymyositis or myocarditis
Oral/nasopharyngeal ulceration
Anaemia and/or thrombocytopaenia
Inflammatory non-septic abdominal, pleural or pericardial effusion
Neurological signs in absence of known disorders
Leukopenia
Antiphospholipid antibodies

Table 1. A diagnosis of SLE requires at least three of these criteria to be met. In this case the criteria met have been highlighted in bold. Ref.  Ettinger, S., Feldman, E. and Côté, E., n.d. 2016. Textbook of veterinary internal medicine. Ch. 205, P.875.

This case was complicated by the history regarding the presumptive treatment for Lyme disease a few years prior, and then subsequent prednisolone based on an allergic response to doxycycline. Following the diagnosis of SLE in this case, the owner sent in some photos of the skin lesions which had developed previously (Figure 2). These lesions were consistent with those commonly seen in SLE and I suspect the previous diagnosis of Lyme disease was in fact an SLE presentation consisting of cutaneous and joint manifestations.

 

Figure 2. Skin lesions present during the Lyme disease suspicion a few years prior. These resemble cutaneous lesions seen in SLE cases.

Luckily steroids were used, albeit for different reasons, and these manifestations went into remission. Glucocorticoids are the cornerstone of Immunosuppressive treatment for SLE, however additional medications can be used alongside these to reduce glucocorticoid-related side effects and aid remission in difficult cases. Mycophenolate is  perhaps one of the most recent and useful additions to veterinary immunosuppressive protocols and was strongly considered. Had the UPC not improved so dramatically in week 1, then mycophenolate would likely have been added and the prednisolone dose reduced. Tapering of immunosuppression should occur over at least 4 months, and it may be useful (as in other immune mediated diseases) to check CRP levels prior to dose reductions. The reported PU/PD in this case with the concurrent normal USG could in part be explained by significant proteinuria and bilirubinuria affecting urine concentration. Clinical disease course for SLE is variable and relapses should be expected.

 

By Joshua White MA VetMB PGCertSAM MRCVS

Referral Medicine Clinician at Bath Veterinary Referrals and RCVS Recognised Advanced Practitioner in Small Animal Medicine.

 

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