1
Title: Thrombotic microangiopathy in adult onset Still's disease: case report and review of the
literature
Titel: Thrombotische Mikroangiopathie bei Kranken mit adultem M.Still: Fallbericht und
Literaturübersicht
INTRODUCTION:
Adult onset Still's disease (AOSD) is a systemic disorder of unknown origin without any
pathognomonic signs. Yamaguchi and the Adult Still's Disease Research Committee studied 90
patients with adult onset Still's disease and proposed eight criteria, which include: fever of ≥ 39ºC
lasting ≥ 1 week, arthralgias lasting ≥ 2 weeks, typical rash, and leukocytosis (≥10 4/ml including
>80% granulocytes) as major signs, and sore throat, lymphadenopathy and/or splenomegaly,
liver dysfunction, and the absence of rheumatoid factor and antinuclear antibodies, as minor
criteria. Five criteria, including at least two major ones, after a strict exclusion process, yielded the
diagnosis with 96.2% sensitivity and 92.1% specificity (1).
Thrombotic microangiopathies (TMA) include several diseases characterized by a
microangiopathic hemolytic anemia, profound thrombocytopenia and organ failure of variable
severity. Together with hemolytic-uremic syndrome (HUS), thrombotic thrombocytopenic purpura
(TTP) belongs to the category of primary (idiopathic) thrombotic microangiopathies, which have to
be distuinguished from secondary TMA forms with underlying or associated disorders, such as:
neoplasia, eclampsia, preeclampsia, autoimmune diseases (antiphospholipid antibody syndrome,
systemic lupus erythematosus, and others), HIV infection, drugs, and others. Thrombotic
thrombocytopenic purpura is associated with a severe deficiency of a von Willebrand factorcleaving protease (termed „ADAMTS13“ as an acronym for a disintegrin and metalloprotease
with thrombospondin-1- like domains), a plasma enzyme specifically involved in the clevage of
unusually large (UL) von Willebrand factor (vWF) multimers into smaller and less adhesive vWF
forms. Failure to degrade these UL-vWL multimers leads to excessive platelet aggregation and
microvascular occlusion. ADAMTS13 deficiency is related to mutation of the encoding gene in
hereditary TTP, whereas in acquired forms it results from autoantibodies that may alter the
2
protein function. This latter finding suggests that acquired idiopathic thrombotic thrombocytopenic
purpura is correspondent to an autoimmune disease. Severe deficiency of ADAMTS13 activity is
present in many, but not all patients with idiopathic TTP, but patients with secondary thrombotic
thrombocytopenic purpura associated with autoimmune disorders may also have a severe
deficiency of ADAMTS13 activity.
Thrombotic thrombocytopenic purpura was originally described by Moschowitz in 1925 as
a disease characterized by unique pathological findings of hyaline thrombi in many organs (2).
Amorosi and Ultmann defined the classic pentad of clinical features: thrombocytopenia,
microangiopathic hemolytic anemia, acute renal impairment, neurologic abnormalities, and fever
(3). The availability of curative treatment has created an urgency for diagnosis and therefore the
stringency of diagnostic criteria has decreased. At the present time, only the dyad of otherwise
unexplained thrombocytopenia and microangiopathic hemolytic anemia (MAHA) are sufficient to
establish the diagnosis of thrombotic microangiopathy and initiate treatment (4).
Both TTP and HUS share similar clinical and pathological findings of hyaline thrombi with
microvascular occlusions in many organs, such as
kidney, brain, or lung. Neurological
manifestations are the predominant features in thrombotic thrombocytopenic purpura, whereas
renal failure predominates in hemolytic uremic syndrome (5).
Based on information from the Oklahoma TTP-HUS Registry, the annual incidence of
patients with a clinical diagnosis of TTP, standardized to United States population, is 11.29/10 6
(6).
3
CASE REPORT:
A 34-year-old caucasian man was admitted to the hospital with a 4-week history of fever,
arthralgias, diffuse muscle pain, and skin rash. At presentation, he did not use any drugs, except
those he had prevously received a day before admittance;
glucocorticoids, antihistamins,
gentamicyn and, calcium, for the skin rash.
Physical examination revealed a temperature of 39ºC, bilateral inflammation of the
carpometacarpal joints, cervical, axillar, and inguinal lyphadenopathy, and a nonpruritic, macular,
confluating rash, behind the ears, on forehead and on the extremities.
Initial laboratory findings: erythrocyte sedimentation rate (ESR) 89mm/h (normal 3-23
mm/h); C-reactive protein 148 mg/l (normal <5.0 mg/l); white blood cell count (WBC) 17.3x10 9/l
(normal 4-10) with a differential count of: 87.8 % neutrophils, 8 % lymphocytes, 2.7 % monocytes,
1.2 % eosinophils, and 0.3 % basophils; red blood cell count (RBC) 4.05x1012/l (normal 4.4-5.8);
normocytic anemia with a hemoglobin of 11.8 g/dl (normal 14-18 g/dl); platelets 561x109/l (normal
140-440). Serum ferritin level was higly elevated (7999 µg/l [normal 10-300 µg/l] or in SI units
17973 pmol/l), protein level was 80g/l (normal 65-85 g/l). The renal function tests were all normal.
Other biochemical values which were revealed to be elevated were: aspartate aminotransferase
(AST 56 U/l), alanine aminotransferase (ALT 79 U/l), lactic acid dehydrogenase (LDH 565 U/l),
gamma-glutamyl transferase (GGT 312 U/l), alcal phosphatase (AP 187 U/l) and a normal total
bilirubin level (normal AST 7-49 U/l, ALT 7-49 U/l, LDH 170-430 U/l, GGT 6-56 U/l, AP 43-120 U/l
). Laboratory evaluation for systemic or malignant diseases : Latex rheumatoid factor, WaalerRose, antibodies to nuclear antigen, dsDNA, cardiolipine, cryoglobulins, complement levels,
serum angiotensine-converting enzyme (ACE), and tumor markers, were negative or within a
normal range.
Bone marrow aspiration, performed from the sternum, showed increased cellularity as
well as increased granulocytopoesis, without other morphological abnormalities. Lymphoid node
aspiration revealed reactive lymph nodes. Cervical lymph node biopsy revealed nonspecific
hyperplasia. Blood and urine cultures were negative. Serological evaluation for hepatitis B and C,
4
HIV infection, and brucellosis was negative. Tuberculosis was ruled out by mycobacteria growth
indicator tube and Amplified Mycobacterium Tuberculosis Direct Test. Serological evaluation for
A. fumigatus and C. neoformans was negative, and a positive small titre of C.albicans was
revealed (indirect hemaglutination 1:320). MSCT of abdomen, echocardiogram, and muscle
biopsy, were unremarkable. Skin biopsy and direct immunofluorescence revealed hypersensitive
reaction. Extensive diagnostic workout excluded infectious, malignant, and hematological disease
as causes of the symptoms.
The patient was diagnosed with adult onset Still's disease, which was affirmed by
Yamaguchi criteria (6) in the presence of 4 major criteria (fever spike, arthralgia, typical rash and
leukocytosis), and 3 minor criteria (lymphadenopathy, liver dysfunction, absence of rheumatoid
factor and antinuclear antibodies). The patient was treated with intravenous glucocorticoids
(methylprednisolonum), and a few days later general status was significantly improved. The fever
had resolved and laboratory findings were in regression. Five months after presentation, the
patient was doing well on low-dose oral glucocorticoids and we initiated chloroquine phosphate
(250 mg/day). After three more months the glucocorticoid therapy was excluded.
Nine months after the initial symptoms of adult Still’s disease, and after four months of
continuous therapy with chloroquine phosphate, the patient was admitted to the hospital for
asymptomatic thrombocytopenia. Physical status was unremarkable except for the pallor of skin
and mucosa. Neurological abnormalities were not observed.
Laboratory evaluation revealed: platelets 27 x109/l, RBC 2.89x1012/l, Hct 0.279 L/L
(normal 0.41-0.55 L/L), Hb 94 g/l (9.4 g/dL), Rtc 133 x109/l (normal 22-97) or in SI units 0.042,
WBC 6.5 x109/l, ESR 23 mm/h, C-reactive protein 4.1 mg/l. LDH, total bilirubin and indirect
bilirubin levels were elevated (LDH 690 U/l [normal 170-430 U/l], total bilirubin 33,2 µmol/l [normal
3.4-20.5 µmol/l], indirect bilirubin 28.3 µmol/l [normal 3.4-15.4 µmol/l]). Haptoglobin level was
decreased to 0.1 g/l (normal 0.3-2 g/l) or in SI units 1 µmol/l. AST, ALT, GGT, AP and serum uric
acid levels were normal. Serum ferritin level was markedly elevated to 1185 µg/L. Blood urea
nitrogen and creatinine levels were within normal range (Cr 90 µmol/l [normal 53-106 µmol/l] and
5
BUN 3.9 mmol/l [normal 3.3-7.8 mmol/l]). The patient’s potassium level was decreased 3.8 mmol/l
(normal 4.1-5.5 mmol/l) but other electrolytes were within normal range. Urine analysis revealed
4-5 red blood cells, and 2-3 leukocytes per high power field, and proteinuria was absent. Urine
culture was negative. Coagulation profile was within normal limits. The serum anticardiolipin
antibodies, Coombs’ tests (direct and indirect), antinuclear and anti dsDNA antibodies, were all
negative.
Peripheral
blood
smear
showed
polychromasia,
aniso/poikylocytosis,
frequent
schistocytes, and a few thrombocytes. A bone marrow aspirate showed hypercellularity of two
series,
erythrocytopoesis
(normoblastic,
partially
macroblastic)
and
an
increase
in
megakaryocytes. Electrocardiogram revealed a right bundle branch block. Thoracic radiography
and abdominal ultrasonography were unremarkable. All the above findings indicated that
microangiopathic hemolytic anemia was not caused by disseminated intravascular coagulation
(DIC) or antiphospholipid syndrome (APS).
The
association
of
unexplained
microangiopathic
hemolytic
anemia
and
thrombocytopenia led to the clinical diagnosis of thrombotic microangiopathy, which is sufficient
to initiate treatment. The patient was promptly treated with daily exchange plasmapheresis (5
sessions), fresh frozen plasma infusions (each approximately 3000 ml), intravenous
glucocorticoids (methylprednisolonum up to 125 mg/day) and acetylsalicylic acid (50 mg/day).
After five plasmapheresis sessions, the platelet count reached 270 x10 9/l and his ferritin and LDH
levels both decreased. The patient was discharged in good condition, on methylprednosolonum
and acetylsalicylic acid. Two years after presentation there was no relapse of thrombotic
microangiopathy.
6
DISCUSSION:
Medline/Pubmed was searched for the years 1966-2008 for an association of adult onset
Still's
disease
and
thrombotic
microangiopathies
using
the
keywords:
thrombotic
thrombocytopenic purpura, hemolytic uremic syndrome, chloroquine, and adult onset Still's
disease.
This case is the fifteenth report in the literature on thrombotic microangiopathies
associated with adult onset Still's disease (Table 1) (7-19). In Table 1, the main characteristics of
patients with TMA and adult onset Still's disease are summarized. The mean age of adult Still's
disease onset in these cases is 31.60 (15-46) years. The interval between onset of thrombotic
microangiopathy and the diagnosis of adult onset Still's disease ranged from 3 days to17 years
and the female/male ratio was 2/1. The mean age of thrombotic microangiopathy onset is 34.70
(15-62) years. Furthermore, in more than half of these patients (8/15) TMA occured within the first
6 months of establishing adult onset Still's disease. In five cases the diagnosis of renal thrombotic
microangiopathy was proven histologically. Eleven of fifteen patients (73%) were treated with
plasmapheresis in addition to glucocorticoid therapy, and among them 8 (73%) had complete
remission, whereas the other 3 had permanent visual impairment and/or digital ischemia. Of the
four patients who were not treated with plasmapheresis, two died, one developed end-stage
renal disease, and one had complete remission. Anticardiolipine antibodies were negative in
90% (9/10) of cases with available data. As far as we know, testing for ADAMTS13 deficiency
was reported in two of these cases. ADAMTS13 activity in one of these reported patients was
decreased to <10 percent of that in the normal control plasma (with a presence of antibodies
against ADAMTS13), and normal in the second patient. In our case, ADAMTS13 activity was not
measured due to technical inability.
To the best of our knowledge, thrombotic microangioapthy has not been described in
literature as a complication of chloroquine treatment. None of the patients reviewed in these 14
cases were treated with chloroquine before or at the time of TMA onset. There is one reported
case of TMA in a patient with rheumatoid arthritis, that occurred after 18 months of therapy with
7
glucocorticoids and chloroquine phosphate, with no known precipitating factor (20). It is possible
that in our case chloroquine phosphate may have been a co-factor for thrombocytopenia but it is
not likely to have induced thrombotic microangiopathy.
Thrombotic microangiopathy as a clinical diagnosis must be made in a timely manner in
order to initiate urgent intervention. Assays for ADAMTS13, and antibodies against ADAMTS13
are not always available, and, even if available, results may not be known for some time. Thus,
while testing for ADAMTS13 deficiency is important for understanding the pathogenesis of the
congenital and acquired causes of this disorder, it should not be used for making the diagnosis,
since delays in initiating treatment may be fatal.
In the era before effective treatment with plasma exchange, 90 percent of patients with
TTP died from systemic microvascular thrombosis that caused cerebral and myocardial
infarctions and renal failure (3). Initial treatment of TMA includes plasma exchange and
glucocorticoids. For adults, plasma exchange is the only treatment for which there are firm data
on its effectiveness (21). If the patient has idiopathic TTP, adjunctive immunosuppressive
treatment with glucocorticoids is appropriate, even without measurements of ADAMTS13 activity
(22). Similarly, in patients whose platelet counts do not increase within several days of plasma
exchange, or those in whom thrombocytopenia recurs when plasma exchange treatments are
diminished or discontinued, addition of glucocorticoids is appropriate (4). Antiplatelet agents, such
as aspirin and dipyridamole, are not effective when given alone for TMA (23). It is possible,
however, that they may be of some benefit when added to plasma exchange (21).
Relapses are rare in patients with thrombotic microangiopathy, except in those with a
severe deficiency of ADAMTS13 activity. Half of such patients may have a relapse, most within a
year (24). In refractory patients, firstly plasma exchange should be intensified (26), and
corticosteroids should be initiated in patients not yet receiving immunosuppressive drugs. Also, if
not previously employed, addition of other modalities may be helpful: prednisone, rituximab,
cyclosporine, cyclophosphamide, azathioprine and intravenous immune globulin (22, 26-28).
Small case series have suggested lower rates of relapse after splenectomy (29).
8
The etiology of adult onset Still’s disease is unknown. Different viral and bacterial agents
have been implicated in the disease pathogenesis. It has also been suggested that AOSD may
be a form of vasculitis mediated by non-necrotizing immune complexes.
The thrombotic microangiopathies are characterized pathologically by the development of
platelet microthrombi that occlude small arterioles and capillaries, and result from a disruption of
the normal platelet–endothelial interface. This can occur either through direct vascular endothelial
wall damage by Shiga toxin (Shiga toxin HUS) or Thomsen–Friedenreich antigen activation
(pneumococcal HUS), or from a defect in normal plasma regulatory systems, such as factor H
deficiency or ADAMTS13 deficiency (constitutional or acquired). However, the pathophysiology of
many of the secondary causes of TMA remains unknown.
The exact pathogenesis of adult onset Still’s
disease associated thrombotic
microangiopathy is unclear and may differ between patients. Unfortunately, only two of the fifteen
patients reviewed here were tested for ADAMTS13 activity, and one of them for antibodies
against ADAMTS13. Because of the relatively small number of reported cases, and insufficient
data on functional studies of ADAMTS13 activity, we may only speculate that the development of
thrombotic microangiopathy in patients with adult onset Still’s disease is not coincidental but may
be the result of a more generalized (auto)immune process.
Further studies are needed,
especially to characterize antibodies against ADAMTS13.
CONCLUSION:
Whether
the association
between
adult
onset
Still's
disease
and thrombotic
microangiopathy is coincidental, or whether they share a similar pathogenic mechanism, remains
unclear. In summary, the purpose of this case report and literature review is to emphasize the
importance of inquiring about clinical and laboratory signs of TMA in patients with adult onset
Still's disease, especially within the first six months of establishing the diagnosis of adult onset
Still’s disease.
9
There is no potential conflict of interest.
10
REFERENCES:
1. Yamaguchi M, Ohta A, Tsunematsu T et al. (1992) Preliminary criteria for classification of adult
Still’s disease. J Rheumatol 19: 424-431
2. Moschowitz E (1925) An acute febrile pleiochromic anemia with hyaline thrombosis of the
terminal arterioles and capillaries. Arch Intern Med 36: 89
3. Amorosi EL, Ultmann JE (1966) Thrombotic thrombocytopenic purpura: report of 16 cases and
review of literature. Medicine 45: 139-159.
4. George JN (2006) Clinical practice. Thrombotic thrombocytopenic purpura. N Engl J Med 354:
1927-1935
5. George JN, Kremer Hovinga JA, Terrell DR, Vesely SK, Lämmle B (2008) The Oklahoma
Thrombotic Thrombocytopenic Purpura-Hemolytic Uremic Syndrome Registry: the Swiss
connection. Eur J Haematol 80(4): 277-286
6. Moake JL (1994) Thrombotic microangiopathies: thrombotic thrombocytopenic purpura and
hemolytic uremic syndrome. 2nd edn. Baltimore: Williams & Wilkins 583-95
7. Masson C, Myhal D, Menard H, Lussier A (1986) Purpura thrombotique thrombopenique fatal
chez une patiente atteinte d’une maladie de Still de l’adulte. Rev Rhum Mal Osteoartric 53: 389391
8. Boki KA, Tsirantonaki MJ, Markakis K, Moutsopoulos HM (1996) Thrombotic thrombocytopenic
purpura in adult Still’s disease. J Rheumatol 23: 385-387
9. Portoles J, de Tomas E, Espinosa A, Gallego E, Nieva GS, Blanco J (1997) Thrombotic
thrombocytopenic purpura and acute renal failure in adult Stll’s disease. Nephrol Dial Transplant
12: 1471-1473
10. Diamond JR (2003) Hemolytic uremic syndrome/thrombotic thrombocytopenic purpura
(HUS/TTP) complicating adult Still’s disease: remission induced with intravenous immunoglobulin
G. J Nephrol 96: 46-49
11
11. Kuo HL, Huang D-F, Lee A-F (2002) Thrombotic microangiopathy in a patient with adult onset
Still’s disease. Rheumatol 8: 276-280
12. Domingues RB, da Gama AM, Caser EB, Musso C, Santos MC (2003) Disseminated cerebral
thrombotic microangiopathy in a patient with adult Still’s disease. Arq Neuropsiquiatr 61: 259-261
13. Perez MG, Rodwig FR Jr. (2003) Chronic relapsing thrombotic thrombocytopenic purpura in
adult onset Still’s disease. South Med J 96: 46-49
14. Quéméneur T, Noel LH, Kyndt X, Droz D, Fleury D et al. (2005) Thrombotic microangiopathy
in adult Still’s disease. Scand J Rheumatol 34: 399-403
15. Hirata S, Okamoto H, Ohta S, Kobashigawa T, Uesato M et al. (2006) Deficient activity of von
Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura in the setting of
adult-onset Still’s disease. Rheumatology (Oxford) 45:1046-1047
16. Robert V, Eszto P, Perrotez J-L, Galzin M, Poussel J-F (2006) Treatment by plasmapheresis
of a thrombotic thrombocytopenic purpura associated to a Still's disease: a case report. Ann Fr
Anesth Reanim 25(5): 532-534
17. Wang H-P, Chen H-A, Liao H-T and Huang D-F (2007) Adult Still’s disease patient developed
thrombotic microangiopathy with diffuse digital gangrene. Scan J Rheumatol 36: 76-78
18. Okwuosa TM, Lee EW, Starosta M, Chohan S, Volkov S et al. (2007) Purtscher-like
retinopathy
in
a
patient
with
adult-onset
Still’s
disease
and
concurrent
thrombotic
thrombocytopenic purpura. Arthritis rheum 57: 182-185
19. Sayarlioglu M, Sayarlioglu H, Ozkaya M, Balakan O, Ali Ucar M (2008) Thrombotic
thrombocytopenic purpura-hemolytic uremic syndrome and adult onset Still’s disease: case report
and review of the literature. Mod rheumatol 18(4): 403-406
20. Kfoury Baz EM, Mahfouz RAR, Masri AFM (1999) Thrombotic thrombocytopenic purpura in a
patient with rheumatoid arthritis treated by plasmapferesis. Ther Apher 3(4): 314-316
12
21. Rock GA, Shumak KH, Buskard NA et al. (1991) Comparison of plasma exchange with
plasma infusion in the treatment of thrombotic thrombocytopenic purpura. N Eng J Med 325 (6):
393-397
22. Aliford SL, Hunt BJ, Rose P, Machin SJ. (2003) Guidelines on the diagnosis and
management of the thrombotic microangiopathic hemolytic anemias. Br J Haematol 120: 556
23. Rosove MH, Ho WG, Goldfinger D (1982) Ineffectiveness of aspirin and dipyridamole in the
treatment of thrombotic thrombocytopenic purpura. Ann Intern Med 96: 27
24. Sadler JE, Moake JL, Miyata T, George JN (2004) Recent advances in thrombotic
thrombocytopenic purpura. Hematology (Am Soc Hematol Educ Program) 407
25. Kahwash E, Lockwood WB (2004) Twice daily plasma exchange in refractory thrombotic
thrombocytopenic purpura. Ther Apher Dial 8: 254-257
26. George JN, Woodson RD, Kiss JE, Kojouri K, Vesely SK (2006) Rituksimab therapy for
thrombotic thrombocytopenic purpura: a proposed study of the Transfusion medicine/Hemostasis
clinical Trials network with a systematic review of rituksimab therapy for immune.mediated
disorders. J Clin Apher 21: 49-56
27. Allan DS, Kovacs MJ, Clark WF (2001) Frequently relapsing thrombotic thrombocytopenic
purpura treated with cytotoxic immunosuppressive therapy. Haematologica 86: 844
28. Ziman A, Mitri M, Klapper E, Pepkowitz SH, Goldfinger D (2005) Combination vincristine and
plasma exchange as initial therapy in patients with thrombotic thrombocytopenic purpura: one
institutions experience and review of the literature. Transfusion 45: 41-49
29. Crowther MA, Heddle N, Hayward CPM, Warkentin T, Kelton JG (1996) Splenectomy done
during hematologic remission to prevent relapse in patients with thrombotic thrombocytopenic
purpura. Ann Intern Med 125: 294-296
13
Table 1:Main characteristics of patients with thrombotic microangiopathy and adult onset Still's disease
Masson
et al.
(7)
Boki et
al.
(8)
Boki
et al.
(8)
Portoles et
al.
(9)
Diamond
(10)
Kuo et
al.
(11)
Domingues
et al.
(12)
Perez
and
Rodwig
(13)
Quéméneur
et al. (14)
Hirata
et al.
(15)
Robert
et al.
(16)
Wang et
al.
(17)
Okwuosa et
al.
(18)
Sayarlioglu
et al.
(19)
This
case
Gender
F
F
F
M
M
M
F
F
M
F
F
F
M
F
F
Age (years)
45
33
28
31
22
23
15
45
42
23
17
42
27
46
34
Fever
+
Arthralgia
and/or
arthritis
Sore throat
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Adenopathies
+
NA
NA
+
NA
+
NA
+
+
NA
NA
-
+
+
-
-
NA
-
-
NA
-
-
NA
-
NA
NA
-
-
+
+
Rash
+
+
+
+
+
+
+
+
+
NA
+
+
+
+
+
Hypertransaminasemia
-
NA
NA
+
NA
+
-
-
+
-
+
NA
+
+
+
Time from
AOSD to
TMA
17
years
3
years
8
years
19
days
4
months
3
months
2
months
3
days
2
weeks
4
years
3
months
7
years
4
weeks
5
years
9
Months
Anticardiolipin
antibodies
NA
-
-
-
NA
-
NA
-
+
NA
NA
-
-
-
-
Serum
creatinine
(µmol/l)
660
123
187
565
942
707
502
HD
865
97
396
442
132
220
90
Diminished
ADAMTS-13
activity
ND
NA
NA
ND
ND
ND
ND
ND
ND
+
-
ND
ND
ND
ND
Kidney biopsy
Renal
TMA
(post
mortem)
ND
ND
Arteriolar
and
glomerular
TMA
Arteriolar
and
glomerular
TMA
ND
Arteriolar
and
glomerular
TMA
ND
Arteriolar
and
glomerular
TMA
ND
ND
ND
ND
ND
ND
Treatment
CS
PP, PI,
CS,
Aspirin
PI,
CS
PP, PI, CS,
HD
PP, PI, CS,
IVIg, HD
PP, CS,
HD
CS, aspirin
CS, IV Ig
CS,
ASA,
PP
PP,
CS, HD
PP, CS
PP, CS, Cy,
vincristine
PP,
CS
PP,
CS
Outcome
Death
CR
CR
PR visual
impairment
CR
creatininemia
88µmol/l
CR
Death
CS,
PP,
HD,
splenectomy,
AZA,
CR
ESRD
CR
CR
PR
diffuse
digital
gangrene
PR visual
impairment
CR
CR
NA not available, ND not done, TMA thrombotic microangiopathy, AOSD adult onset Still's disease, HD hemodyalisis, CS corticosteroids, PP plasmapheresis, PI plasmainfusion, IV Ig intravenous immunoglobulins, AZA azathioprine,
Cy cyclophosphamide, CR complete remission, PR partial remission, ESRD end stage renal disease