Acute Renal Failure during Progressive Systemic Sclerosis in the Regional University Teaching Hospital of Brest-La Cavale Blanche (France)

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Open Journal of Rheumatology and Autoimmune Diseases, 2017, 7, 158-166
http://www.scirp.org/journal/ojra
ISSN Online: 2164-005X
ISSN Print: 2163-9914
DOI: 10.4236/ojra.2017.73016 Aug. 18, 2017
Acute Renal Failure during Progressive
Systemic Sclerosis in the Regional University
Teaching Hospital of Brest-La Cavale Blanche
(France)
Comlan Albert Dovonou1, Cossi Adébayo Alassani1*, Séraphin Ahoui1, Lauren Gueguen2,
Arthur Capdeville2, Elie Cornec-Le Gall2, Laurent Doucet2, Yannick Le Meur2
1Borgou Regional University Teaching Hospital, Parakou, Benin
2Regional University Teaching Hospital of Brest-La Cavale Blanche, Brest, France
Abstract
Systemic scleroderma is a rare disease in which visceral manifestations o
c-
cur,
particularly peripheral vascular, digestive, cardiopulmonary and renal.
It is pathology
with a predilection for women. The present clinical case is
that of a man with the renal complications of scleroderma and the difficu
l-
ties of the treatment even in the
developed countries like France. In the
present case, the management of this disease required a high dose of cort
i-
costeroid therapy and extra-renal purification. Early detection of complic
a-
tions through a minimal clinical examination supplemented with par
aclinic
tests has proved necessary.
Keywords
Systemic Sclerosis, Acute Renal Failure, Brest, France
1. Introduction
Progressive systemic sclerosis is a rare disease during which visceral manifesta-
tions occur, in particular vascular peripheral, digestive, cardiopulmonary and
renal ones [1] [2].
It is characterized by microcirculation abnormalities and scleroderma and/or
visceral sclerosis.
Progressive systemic sclerosis predominantly affects women (3 to 8 women vs.
1 man). Peak frequency is between 45 and 64 years. The prevalence of sclero-
derma is still not well understood; it is estimated at more than 200 million inha-
How to cite this paper:
Dovonou, C.A.,
Alassani
, C.A., Ahoui, S., Gueguen, L
.,
Capdeville
, A., Gall, E.C.-L., Doucet, L. and
Meur
, Y.L. (2017)
Acute Renal Failure
during Progressive Systemic Sclerosis in the
Regional University Teaching Hospital of
Brest
-La Cavale Blanche (France).
Open
Journal of Rheumatology and Autoimmune
Diseases
,
7
, 158-166.
https:
//doi.org/10.4236/ojra.2017.73016
Received:
June 21, 2017
Accepted:
August 15, 2017
Published:
August 18, 2017
Copyright © 201
7 by authors and
Scientific
Research Publishing Inc.
This work is licensed under the Creative
Commons Attribution
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License (CC BY
4.0).
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Open Access

C. A. Dovonou et al.
159
bitants in the United States and Oceania, and at 20 to 80 million inhabitants in
Asia. In France, this prevalence is 158 million inhabitants [1].
One of the fearsome complications of progressive systemic sclerosis is organic
acute renal failure which is rapidly progressive; it is also known as renal crisis. It
is characterized by its rapid onset with malignant hypertension and mild prote-
inuria most often on the occasion of a heart failure [3] [4].
Its occurrence is life-threatening for the patients and reduces patients’ survival
with progressive systemic sclerosis; it requires a quick management in the he-
modialysis unit. Its concurrent progression with an interstitial pneumonia and
occurrence of pulmonary arterial hypertension increases mortality rate between
12% and 14%. Until now, no treatment has proved to be effective on survival.
But there is still hope; non-drug therapies like physical rehabilitation are under
assessment [5].
The objective of this presentation is to guide any practitioner towards diagno-
sis of renal crisis in the face of sudden multiple organ failure resulting from pro-
gressive systemic sclerosis.
2. Case Report
2.1. Mr. MG Aged 54 Years
He was admitted to the surgical intensive care unit of the CHRU La Cavale
Blanche of Brest on 12 September, 2015 for decompensated diabetic ketoacido-
sis, acute renal failure and hemolytic anemia.
2.2. History
• Medical history
- Type 1 Diabetes since the age of 15.
- Hypothyroidism.
- Hypercholesterolemia treated.
- Tumor of free edge of the tongue treated by chemoradiotherapy—in 2014; in
remission since December 2014.
- Possible exposure to asbestos, notion of asbestosis on last chest scans carried
out.
- Left pleural effusion in 2014 with pachypleuritis which is not specific to ana-
tomic pathology, of lymphocytic appearance.
- Inflammatory right pleural effusion with mesothelial cells in 2015.
• Surgical:
- Appendectomy.
• Allergy: unknown
• Ongoing treatment on admission:
- Prednisone 40 mg in the morning.
- Pravastatin 40 mg, 1 tablet every evening.
- Levothyrox 75 μg in the morning.
- Sulfarlem 3 tablets/day.
- Levemir and Novorapid insulin.

C. A. Dovonou et al.
160
2.3. History of the Disease
Since May 2015 Mr. MG has been presenting with recurrent pleural effusions
and lower extremity edema without initial etiology identified. Corticotherapy
was set up on May 20, 2015 with intake of Prednisone 40 mg in the morning.
Pleural punctures carried out resulted in inflammatory pleural fluid rich in eo-
sinophils, associated with a biological inflammatory syndrome, in a patient with
history of auto-immunity recently discovered.
These are positive antinuclear antibodies, positive anti-SSB and positive anti-
Scl 70.
The etiology mentioned was progressive systemic sclerosis. No other caus-
es/factors of heart disease or renal failure were mentioned.
On 10 September, 2015 the patient was admitted again to a private clinic for
deterioration of the general condition. He presented at that time with an ana-
sarca picture with bilateral pleural effusion, pericardial effusion and strip of as-
cites, as well as synovitis in both wrists.
2.4. Skin is Sclerotic
The biological test finds out an inflammatory syndrome, a non obstructive and
rapidly progressive acute renal failure (ultrasound of urinary tract performed)
with elevated creatinine of 250 μmol/L on admission for a reference value esti-
mated at 45 μmol/L early in August 2015. Proteinuria is estimated at 1.27 g/L.
Complete blood count showed hemolytic anemia, lactate dehydrogenase (LDH)
was estimated at 1100 UI/L and Haptoglobin has collapsed (<0.5 g/dL). There is
also an unbalanced hypothyroidism (TSH at 30) which justifies the increase of
Levothyroxine from 75 to 100 μg/day.
In addition to this picture of non obstructive acute renal failure with glome-
rular appearance and anasarca picture, there was a decompensation of his di-
abetes with a major ketoacidosis. Blood-pH was estimated at 7.18. An intraven-
ous insulin therapy was put in place. Therefore, he was transferred to the surgic-
al intensive care unit for further care.
On admission on 12 September, 2015 Mr. MG was confused in time but
oriented in the space. A psychomotor retardation was noted and there was no
sensorimotor deficit. Mr. MG was eupneic under 2 l/mn of O2. The vesicular
murmur was reduced to the two bases. Hemodynamics was rather stable on the
hypertensive side; blood pressure was estimated at 160/80 mm Hg. Heart rate
(HR) was 100 pulses/mn.
Heart sounds were regular and breathless. There was no sign of peripheral
hypoperfusion. There were peripheral edemas. There were no other signs of
right heart failure.
Abdomen was flexible and defenseless; there were hydroaeric sounds.
The patient showed acute renal failure with oliguria, urea at 25.8 mmol/L and
elevated creatinine at 360 μmol/L.
pH was at 7.18, PaCO2 at 104 mmHg.
There were anemia at 7.5 g/dl and blood platelets at 198,000 elts/mm3 (refer-

C. A. Dovonou et al.
161
ence blood platelets one month before at 600,000 elts/mm3).
Haptoglobin has collapsed; presence of Schizocytes. Coombs test was negative.
Initial practical conduct in the unit consists of:
• Insulin therapy INSE within the framework of ketoacidosis.
• Adequate hydratation.
• Hemodynamic and respiratory monitoring.
• Monitoring of renal function.
• Setting up of probabilistic antibiotic therapy with Tazocilline, Vancomycin
and Amiklin.
On 13 September, 2015 Mr. MG presented with abrupt desaturation at 70%,
crackling sounds in the two fields on lung auscultation. Facing that acute pul-
monary edema, the patient received Lasilix at the dose of 1 mg/Kg, Risordan as a
bolus (8 mg altogether) and hemofiltration on an emergency basis on heparin
therapy to enable quick clinical improvement.
2.5. Outcome in the Unit
Mr. MG is dialyzed in the unit since 13 September, 2015.
In this context of acute renal failure associated with arterial hypertension and
mechanic hemolytic anemia, a renal ultrasound was performed by eliminating
obstruction.
Immunological examination was carried out; it highlighted anti-SSB positive
antibodies, anti-ScL70 positive antibodies; in contrast Anti Neutrophil Cytop-
lasmic Antibody Auto-anticorps (ANCA) are negative.
In his recent history, Mr. MG reports the appearance of Raynaud’s syndrome
for about one year, the onset of scleroderma with distal predominance and scle-
rosis of face for approximately two months and gastro-esophageal reflux.
In the face of this picture, the diagnosis of renal failure with thrombotic micro-
angiopathy of hemolytic and atypical uremic category syndrome is raised.
On 15 September, 2015 a puncture or renal biopsy was performed; results are
compatible with vascular nephropathy, secondary lesions, malignant hyperten-
sion and thrombotic micro-angiopathy (Figures 1-3).
: Fibrinoid necrosis of an arteriole.
Figure 1. Fibrinoid necrosis of an arteriole.

C. A. Dovonou et al.
162
: Glomerulus seat of fibrin microthrombi.
Figure 2. Glomerulus with fibrin microthrombi.
: Arteriole in the form of onion bulb; : Glomerulus.
Figure 3. Arteriole in the form of onion bulb.
On 17 September, 2015 the diagnosis of scleroderma renal crisis facilitated by
introduction of corticoids at 40 mg/day in that patient carrying progressive sys-
temic sclerosis since May 2015, was retained. Diagnosis was confirmed in the
internal medicine unit.
2.6. Actions Taken
• Corticotherapy is stopped on 17 September, 2015.
• Setting up of treatment by Angiotensin Converting Enzyme Inhibitor for
strict control of blood pressure with an objective lower than 120/60 mmHg.
• Continuation of IV Loxen at 2 mg/h and Eupressyl 60 mg × 2/day, necessary
to get a satisfactory blood pressure goal or target. Eupressyl will be increased
to 90 mg × 2/day in order to stabilize blood pressure targets.
• Patient is subject to depletion on average at 2500 ml/24hours. Besides, there
is no associated ionic disorder.
• Facing hypothermia on patient’s admission, associated with significant in-

C. A. Dovonou et al.
163
flammatory syndrome with high procalcitonin level at 9.9 ug/l, a hyperleu-
kocytosis at 40 Giga/l, a triple probabilistic antibiotic therapy with Tazocil-
line, Vancomycin and Amikacin was put in place; blood cultures performed
on the venous-access port are returned positive in two bottles of Staphylo-
coccus epidermidis, peripheral blood cultures are negative. In this context,
the venous-access port is withdrawn on 17 September, 2015. The patient will
remain apyretic during all the hospitalization period. Triple therapy is
stopped on 20 September, 2015.
2.7. Outcome
• Systemically: the patient shows Sjögren’s syndrome with dry eyes and dry
mouth. Scleroderma is predominant in the hands with impossibility of clen-
ching wrists. Hypo-pigmentation signs in the interphalangeal articulations of
the two hands and arthralgia affecting wrists are noted.
• At neurological level, the patient is properly oriented in time and space, no
sensorimotor deficit was observed.
• As far as respiration is concerned: the patient remained with eupnoea in am-
bient air. Examination pointed out right pleural effusion syndrome con-
firmed by ultrasound; it will be evacuated. Puncture fluid is compatible with
transsudat; there is no abnormal cell, no germ.
• As regards hemodynamics:
Blood pressure is controlled under Angiotensin Converting Enzyme Inhibitor,
Ramipril 2.5 mg/day which will be progressively increased to 10 mg/day and
Urapidil 90 mg × 2/day.
No sign of peripheral hypoperfusion was observed. Heart auscultation re-
mained normal. Heart ultrasound is performed; it did not reveal pulmonary
hypertension.
• At regards digestion:
Abdomen remained flexible, depressible and painless. Mr. MG presented with
chronic diarrhea. In the context of hemolytic and uremic syndrome, a search for
Shiga toxin is undertaken in the feces and for Escherichia coli 0157H7; results
are negative.
Gastrointestinal endoscopy is done: findings are Stage 0 esophagitis, erythe-
matous gastritis with clear gastric fluid and bulbitis. Duodenum is normal.
Biologically: anemia is persistent, with hemoglobin level at 8.3 g/dl, blood
platelets at 142,000/mm3; presence of schizocytes is on the decline. Haptoglobin
is still very low.
Hemoglobin level as at 13 October, 2015 is estimated at 10.1 g/dl.
• The rest of clinical examination is still normal.
The consent of Mr. MG for the publication of this case was obtained.
3. Discussion
The clinical case of Mr. MG raises some reactions. Scleroderma is a rare disease
during which visceral manifestations occur, in particular vascular peripheral,

C. A. Dovonou et al.
164
digestive, cardiopulmonary and renal ones [6] [7]. It is characterized by micro-
circulation abnormities and lesions in scleroderma and/or visceral sclerosis.
Sometimes, those sclerotic lesions may be moderate and distal, involving only
fingers, toes and circumference of mouth or sometimes very extended above
knees, elbows and even trunk. This disease mainly affects women (3 to 8 women
vs. 1 man). The age group from 45 to 64 years is the most affected [8] [9].
Its pathophysiology is complex and still not well known, including dysfunc-
tions of endothelial cells, fibroblasts and lymphocytes. The malfunction of fi-
broblasts is characterized by uncontrolled activation enabling the synthesis of
excess extra-cellular matrix. The endothelial cells synthesize excess endothelin-1
which is a powerful vasoconstrictor. Antinuclear antibodies are detectable in the
serum of most patients, directed against nuclear proteins or recognizing the en-
dothelial cells and/or fibroblasts. Oxidative stress seems to play a major role in
scleroderma pathogenesis [10] [11].
All those abnormalities may be associated with genetic predisposition.
Mr. MG is 54 years old; he has been suffering from scleroderma, polyarthral-
gia and Raynaud’s syndrome for some years. He also has visceral and cardi-
opulmonary dysfunctions with heart decompensation and bilateral pleu-
ro-pneumopathy complicated by episodes of desaturation. This confirms sys-
temic scleroderma diagnosis.
Scleroderma renal crisis is a complication of systemic scleroderma, abrupt
onset with arterial hypertension, grade III or IV hypertensive retinopathy, in-
creased peripheral activity of rennin which may reach twice the normal thre-
shold and rapid deterioration in renal function in one month [10] [12]. Such is
the case in Mr. MG whose elevated creatinine increased from 45 μmol/L in early
August 2015 to 250 μmol/L on 10 September, 2015 and to 360 μmol/L on 12
September, 2015. Sometimes, this renal crisis may develop with few signs or al-
most silently. [4]. It is important to identify it; early diagnosis and quick man-
agement are the only means of favorable outcome. Renal crisis occurs very
quickly after about three years of progression of the initial disease [12].
The immunological examination of this patient confirms the existence of a
connective tissue disease (CTD); in this case it is scleroderma. It would have
been necessary to measure anti-RNA polymerase III antibodies (Pol3) so as to
confirm that diagnosis. Our center does not carry out this examination. In lite-
rature, all the authors agree on the specificity of Pol3 in the scleroderma renal
crisis [13] [14]. The identification of POLR3A sub-unit which is a mutation of
Anti-RNA Polymerase III antibody in a patient is an indication of the concur-
rent outcome of an underlying cancer. Considering the bundle of clinical, parac-
linical and therapeutic arguments, scleroderma renal crisis was retained [15]
[16].
As the patient was put on Angiotensin Converting Enzyme Inhibitor and he-
modialysis in accordance with literature data, outcome was adequate. In general,
remission is complete after 2 years of renal clearance; beyond this length of time,
kidney transplantation must be contemplated. Actually, early treatment is a de-

C. A. Dovonou et al.
165
termining factor for patients’ survival and is now the key therapeutic objective
during progressive systemic sclerosis [17] [18].
4. Conclusion
Progressive systemic sclerosis is a severe form that causes significant reduction
of survival of patients with scleroderma. This severity is associated with occur-
rence during disease progression of visceral disorders, more particularly severe
interstitial pneumonia and pulmonary hypertension which may cause death in
the patients. Scleroderma renal crisis is a dramatic picture facilitated by intro-
ducing in the scleroderma treatment a high dose corticotherapy outcome of
which is quickly favorable on Angiotensin Converting Enzyme Inhibitor, and
extrarenal excretion after stopping corticoids. The severity of those visceral dis-
orders justifies their systematic and repeated detection through oriented histo-
ry-taking, clinical examination and further tests.
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