Kidney Damage during Sharp’s Syndrome: About Two Cases

Context: The coexistence in the same patient of a mixed connectivitis or Sharp’s syndrome is a rare eventuality. Objective: To underline the presence of this mixed connectivitis in our practice, whose prevalence remains un-known, particularly in Africa and more precisely in Mali. Case Presenta-tions: We report two cases of Sharp’s syndrome in a 48-year-old man and a 40-year-old woman with impaired renal function. The picture achieved associated massive proteinuria, hypoalbuminemia, moderate renal failure and edematous syndrome in men. In women, the picture was associated with ac-celerated to malignant hypertension and severe renal failure. There were no osteoarticular manifestations and the diagnosis of Sharp’s syndrome was based on the presence of high levels of antibodies to U1RNP. Therapeutic management has been that of predominantly associated connective tissue disease (systemic lupus erythematosus). Conclusion: Mixed connectivitis or Sharp’s syndrome is increasingly recognized as a separate entity thanks to advances in molecular biology. Its prevalence is low in sub-Saharan African countries with renal disease that manifests itself as proteinuria or nephrotic syndrome associated with microscopic hematuria, renal failure, and hypertension. This renal impairment is more likely to occur in severe forms of the disease. 50 on the Doppler


Introduction
Beside the typical forms of connectivity, Sharp reported 25 cases of patients with signs common to systemic lupus erythematosus, rheumatoid arthritis, scleroderma and polymyositis [1]. Immunologically, anti-RNP antibodies and much less frequently double-stranded DNA Ac are consistently found. Serum complement is normal or elevated. This syndrome has been called Sharp's syndrome or mixed connectivitis. Renal damage is reported to be common during Sharp syndrome, ranging from 5% to 40% in adult series and 50% in children [1]. On the other hand, the list of anti-RNP antibodies or the complement is not different between patients who will develop kidney disease and those who will not [2]. This description has given rise to many controversies that are still relevant today, as the evolution of most patients rarely evolves towards a mixed picture, but rather towards a deterministic connectivity. Anglo-Saxon authors use the term UCTD (undifferentiated connective tissue disease) to designate this syndrome [3]. For M.F. Kahn, the term "Sharp syndrome" refers to the initial syndrome, while suggesting that the subsequent picture will be an entanglement of the present syndrome and a specific connectivitis [4].
We report two observations with the presence of complicated Sharp's syndrome in a 48-year-old man and a 40-year-old woman with impaired renal function.
The objective of these observations is to highlight the presence of this mixed connectivitis in our practice, the prevalence of which remains unknown, particularly in Africa and more specifically in Mali.

Observation N˚1
Mr. C.M., 48 years old Malian, Bambara, uninsured trader, consulted during 2019 for edematous syndrome. When questioned, the patient complained of facial puffiness, oedema of the lower limbs, bilateral lumbar pain and dyspnea of effort. High blood pressure was diagnosed about a year ago.
On admission, he was apyretic with a blood pressure of 160/80 mmHg. On examination, localized oedemas on the lower limbs, painlessly keeping the cup, were noted, as well as conjunctival pallor. Pulmonary and cardiac examination was normal. Elsewhere the examination was without particularity. The search for proteinuria, haematuria, glycosuria, nitrites with the urinary strip was not carried out for lack of means.

Observation N˚2
Mrs with an improvement of hemoglobin level to 12g/dl, proteinuria of 24H at 0.6g, creatinine level at 115 µmol/l without any complaints. However, due to financial difficulties, adherence to treatment is not totally assured. As for the second observation (hypertensive retinopathy stage III and visceral damage) the evolution was less favorable despite treatment. Currently, she is in an iterative dialysis program with stabilization of the clinical state. Sharp [5]  between 1998 and 2000 in Côte d'Ivoire [16]. Lutalo also reported 2 cases in Zimbawe in 1985 with more of an overlap syndrome profile [17]. All these works suggest that mixed connectivitis is a rare entity in black people in general and in Our patients were diagnosed solely on the basis of serological criteria, i.e., the presence of high titer anti-ribonucleoprotein (RNP) antibodies associated with renal manifestations.

Discussion
Renal impairment is reported to be frequent in Sharp syndrome: 5% -40% in adult series and 50% in children [22]. However, in a recent series of 32 patients followed for 65 months, no patient developed renal impairment. The difference in the prevalence of renal impairment between series is due to the vagueness in the definition of the disease itself and in the definition of renal impairment [23].
For example, forms similar to systemic lupus erythematosus or systemic scleroderma may have corresponding nephrological damage, including scleroderma kidney attacks [22]. In addition to the presence of high levels of anti-U1RNP Ac in both our patients, there was the presence of anti-Sm Ac in the male patient and anti-SSA Ac in the female patient, which could explain the renal impairment. In the literature renal manifestations were associated with proteinuria with or without nephrotic syndrome associated with microscopic hematuria.
Renal failure and hypertension are rare [23]. Our male patient presents massive proteinuria with hypoalbuminemia. This nephrotic syndrome is multifactorial, characterized by the presence of high levels of antibodies to U1RNP and Ac anti Sm, positive hepatitis C serology, and the presence of Ac anti-treponemapallidum, which can be complicated by renal impairment, hence the interest of renal puncture biopsy for precision histological elements. As for our patient, she presented a malignant arterial hypertension (exudates, microhemorrhages, papilloedema) complicated by renal and cardiac damage. She also showed some signs of hemolysis (thrombocytopenia, increased LDH, presence of schizocytes). Although all types of glomerular involvement have been described, extramembranous glomerulonephritis seems to be the most common type of glomerulonephritis in Sharp syndrome/mixed connectivitis [2] [24]. The absence of renal puncture biopsy in our patients did not allow us to make the histological diagnosis.

Conclusion
Mixed connectivitis or Sharp's syndrome is increasingly recognized as a separate entity thanks to advances in molecular biology. Its prevalence is low in sub-Saharan African countries with renal disease that presents with proteinuria or nephrotic syndrome associated with microscopic hematuria, renal failure, and hypertension. This kidney damage is more likely to occur in severe forms of the disease.