Renal ultrasound showed normal kidneys dimensions, with maintained differentiation and thickness of the parenchyma, without pielo-caliceal dilatation.

The patient started large spectrum antibiotics for the upper respiratory tract infection, but the fever persisted. Urgent haemodialysis was also performed due to severe impairment of the renal function, with oliguria and fluid overload.

She started immunosuppressive treatment with 3 pulses of methylprednisolone 500 mg IV and 3 administrations of cyclophosphamide 0.5 g/m2/month, with an interval of three months. After that, the patient remained afebrile.

She was discharged at the end of 3 weeks of hospitalization, medicated with prednisolone 1mg/kg, isoniazid, pyridoxine, calcium carbonate, esomeprazole and darbepoetin, She kept on a regular haemodialysis programme, three times a week. Three months after the hospitalization, partial recuperation of the renal function was verified, leading to haemodialysis discontinuation. In November 2010, mycophenolate  mofetil 500 mg twice a day was started.

At present, the patient is asymptomatic, with creatinine clearance greater than 90ml/min, negative anti-dsDNAand ANA, normal C3 complement, while maintaining proteinuria less than 1g/24h and no haematuria.

DISCUSSION

We present a case of RA with symmetrical and erosive joint involvement of the extremities, in a 30-year-old female patient, followed, after a long period, by clinical and laboratory features of lupus.

The last diagnosis was based on pleural effusion, renal and haematological involvement, positive ANA and anti-dsDNA. According to the literature, the combination of these diseases corresponds to rhupus^4,5.

This case is singular, because in the cases of rhupus, usually, we find cutaneous and haematological abnormalities, and not such severe renal involvement.

Systemic lupus erythematosus is a systemic autoimmune disease, in which the tissues and the cells are damaged by antibodies and immunocomplexes.

The female gender is the most affected (90%), with a peak incidence between the ages of 25-35^1-3.

The aetiology and pathogenesis of SLE remain uncertain, however, it is known that the disease is caused by the interaction of the genes that are found in the HLA region, particularly HLA class II DR and DQ and class III encoding the complement C2 and C4, and environment factors, that result in an abnormal immunological response, with incessant production of antibodies and formation of immunocomplexes^1,3.

These fixate in the target tissues, destroying them, releasing chemotaxins, proteolytic enzymes and vasoactive peptides, causing a chronic inflammation. Many antibodies take part in this phenomenon, among them: DNA antibodies (ANA, antidsDNA antibodies), anti-RNA (anti-Sm, anti-RNP, anti-SSB, anti-SSA), anti-histone antibodies, antiphospholipid, anti-erythrocyte, anti-platelet and anti-ribossomic^1-3.

The SLE manifestations are different, depending on the organ or tissue affected. These can include skin, kidney, joints, vessels, eyes and neurological, pulmonary, cardiac, haematological and gastrointestinal systems^1-3. Renal manifestations occur in 40-85% of patients, due to immunocomplex deposition in the glomeruli. These may present as changes in urinary sediment (proteinuria, microscopic haematuria), nephritic syndrome, nephrotic syndrome, failure³.

Lupus nephritis is an immune complex glomerulonephritis with decreased levels of C3, with positive ANA and anti-dsDNAantibodies most of the times¹⁰.

Commonly, at age 20’s the survival rate of SLE rounds 75%, however, the occurrence of severe lupus nephritis is associated with poor prognosis, achieving a mortality of about 50% in 10 years¹⁰.

Joint involvement is typically the first manifestation that occurs in SLE, with multiple presentations that include arthralgia, non-deforming arthritis, and deforming arthritis with or without erosions. The non-deforming arthritis consists on intermittent polyarthritis, slight to disabling, characterized by soft tissue swelling and joint pain⁵. The term “Jaccoud arthropathy” was defined by Brywaters (1950), when he noticed that the deforming arthritis in patients with SLE was very similar to the arthritis that Jaccoud described in 1869, associated to the rheumatic fever⁵.

This disease is characterized by non-erosive deformations, subluxation of the metacarpophalangeal joints with ulnar deviation, and hyperextension of the proximal interphalangeal joints, which are all reversible at an early stage⁵.

By contrast, the arthritis found in RA is symmetrical, erosive, and rarely affect the distal interphalangeal joints. Some of the changes that can be found in the joints are: ulnar deviation of the fingers through the wrist abduction and injury of the metacarpal phalangeal (MCP); fingers in “swan lap” due to the flexion of MCP, hyperextension of the proximal interphalangeal (PIP) and flexion of the distal interphalangeal (DIP), “buttonhole” fingers due to the flexion of PIP and hyperextension of DIP; Z thumbby flexion of MCP and hyperextension of the interphalangeal; finger pending due to the ruptureof the extensor tendon¹¹.

Despite the highly detailed characterization of these two syndromes as to separate entities, sometimes there are cases in which the characteristics of SLE and RA are found together^6,7.

In 1969, Kantor published a case of erosive arthropathy in a patient with SLE and RA⁶.In the 1970s, Schur used the designation “rhupus” for the first time to define a new entity that had features of SLE and RA⁷.From this date, this definition has been discussed many times. Is Rhupus an independent entity, an overlapping syndrome, or a subtype of SLE^8,9?

The truth is that the prevalence of erosive arthritis in patients with SLE is low, about 1-5%⁹. Fernandez, et al., when reviewing and observing 8 cases with rhupus, stated that this entity is a subtype of SLE. They associated, with high probability, the antibody anti-RA33 with the presence of erosive arthritis in SLE⁸.

On the other hand, Amezcua-Guerra,et al. found high titrations of anti-CCP, defending that this entity consists in an overlapping syndrome⁹. Amezcua-Guerra, in 2009, affirmed that there is no doubt that rupus belongs to the spectrum of SLE, however, he questioned if these patients also have RA. There is evidence that sustains the existence of rhupus as an overlapping syndrome. The author used three arguments to explain his point of view. The first one is the presence of anti CCP, which is very specific to RA; the second is the established association between the risk of RA and the MHC II molecules, which share the same sequence of amino acids in the 72nd – 74thposition of the β chain. These shared epitope (SE) alleles connect preferentially to the peptides that have as a component the citrulline amino acid, and have an effect on the production of anti-CCP in RA. It is possible that the association between SLE and erosive arthritis is due to the indirect effect mediated by antibodies against different citrullinated proteins. Sixty-seven per cent of patients with SLE and erosive arthritis are carriers of SE alleles, in contrast with the 22% of patients with non-erosive arthritis, and the presence of two copies of SE alleles increase by 8 the risk of erosive arthritis in SLE. The third argument involves CRP. This directly correlates with the activity in RA, with a deficient production in SLE. However, in rhupus a normal production of CRP was verified. The author concluded that the criteria of SLE and RA should be re-evaluated in the light of new discoveries, and remark that autoimmune diseases are classified and artificially differentiated by barriers created by doctors and investigators¹².

CONCLUSION

Rhupus is the most probable diagnosis to the presented case. It is very interesting to see that the disease extends for a very long period of time (26 years), and the signs and symptoms are different in different periods of time.

This case is rare, because in the cases of rhupus, usually, we find cutaneous and haematological abnormalities, and not such severe renal involvement. In this patient with severe renal impairment, with an adequate immunosuppressive strategy, renal function recovery was possible which led to an improvement of the quality of life of a young female, already limited by the articular component of the disease.

Although the diagnosis of SLE and RA is relatively frequent, rhupus is a rare entity. Its place in autoimmune pathologies as a distinct entity or an overlapping syndrome is still uncertain.

References