Aim:  We report a rare case of Wegener granulomatosis  eventually ending in catastrophic antiphospholipid syndrome.

 

Method:  A 42 year- old female patient, diagnosed and treated for Wegener granulomatosis  since 14 y.o., suddenly manifests a left orbital pseudotumor. The clinical exam revealed: left orbital panniculitis, visual acuity loss, papillary oedema in the left eye and limited motility of the left  globe.

 

Results: The investigations demonstrated the presence of the infectious  Lysteria monocitogenes causing orbital pseudotumor . The treatment targeted both the infectious cause and the Wegener granulomatosis. The outcome was the anatomic recovery of the left globe, but the function was lost.

 

Discussion:  Besides the granulomatosis vasculitis, the presence of the microorganisms also induces increased antiphospholipid antibodies (APLA). APLA induce cell  humoral  immunity disorders, as a consequence of the infectious process. 

 

Conclusion: The infection represents the mutual trigger both for the increase of cANCA and for the exacerbation of the thrombosis mechanism due to APLA,  leading finally to a catastrophic antiphospholipid syndrome.

The evolution pattern of the antiphospholipid antibodies leads to the catastrophic systemic inflammatory syndrome, due to the second infection impossible to controle two years  after.

 

History

• January 2006 - Fig.1, Fig.2, Fig.3
  Patient M.F., 42 y.o., with:
  - Left orbital panniculitis
  - VA decreased in OS
  - PAPILLARY STASIS OS
  - Motility affected in OS
  - DIPLOPIA

• 1992
  

  Operated nasal septum deviation, subcutaneous nodules, partial nasal septum lesion, haemorrhagic lesions strictly around nasal septum. Maxillary sinus puncture – bacteriologic exam: pyocyaneus

    DIAGNOSIS: Granulomatosis Wegener

• 1993
  - biopsy + pulmonary exam    cyclophosphamide 200mg
• 1994
  - one hospitalization cyclophosphamide 150 mg
• 1995
  - one hospitalization cyclophosphamide 100mg
• 1997 +1998
  - cyclophosphamide 50mg
• 1997-2001
  - Control in the Infectious diseases department
• 2001-2004
  - without cyclophosphamide – cutaneous and sinus lesions
• 2005
  - PAS 12tb, biseptolum on her own account for necrotic cutaneous lesions over elbows and knees
• 2005
  - left hallux nail necrosis and Raynaud syndrome, recurrent necrotic cutaneous vesicles, splenic infarctions, HTN (max 170/110mmHg), left breast nodule 2cm without axillary ganglion, APS?
• 2006 - Fig.4
  - aspect of left inflammatory orbital pseudotumor
• 2006 - Fig.5, Fig.6
  - aspect of left inflammatory orbital pseudotumor

*Spontaneous orbital haematoma. Martinez Devesa P. Journal of laryngology and otology, 2002, vol.116, no11, pp.960-961

 

 

ESR = 40 mm/1hour, fibrinogen = 519, thrombocytes = 450,000 Hb = 11,9%; The tuberculin skin test (IDR) = + 15, c-ANCA = normal, C-reactive protein = normal

• Lungs: pulmonary x-ray – enlarged right hilar
• Kidneys : AP max = 170mmHg, creatinine = normal
• Left breast nodule 2cm without axillary ganglion, normal left breast mammography
• Recurrent necrotic cutaneous vesicles
  LA = positive, aß2GPI = 36UE, Protein C = 85% (N > 75%)
  Protein S = 62% (N > 65%), AT III = 118% (N > 80%)
• ELISA for listeria IgM = 1,305 (N =0,500)
• PARACLINICAL : MRI
• Difuse infiltrative- edematous modific. (granulation tissue?) at the level of the left periorbitary soft tissue and wall, infiltrating extrinsic ocular muscles, lacrimal gland and partly retroorbitary fat tissue.
• Left ethmoidal and frontosphenoidal sinusitis - Fig.7

 

ENT Consultation    – Prof. Dr. C. Sarafoleanu Fig.8

• Left anteroposterior ethmoidotomy to achieve left orbital decompression hoping to save visual function in OS.
• Anatomo-pathological examination: confirms the specific aspect of Wegener Granulomatosis.

Fig.9 - The 4th day after decompression surgery

Fig.10 - The 8th day after decompression surgery

 

Stage diagnosis:

• CLINICAL
  

  Left inflammatory orbital pseudotumor  afecting all orbitary elements:

     - optic nerve,    - oculomotory muscles,    - cellulitis,    - pannicullitis

     - vessels → hyperviscosy syndrome by rheological mechanism and affectation of vascular endothelium

• PARACLINICAL
  - biological
  - MRI
  - anatomopathological exam

Wegener disease with pluriorganic implication +
ANTIPHOSPHOLIPID SYNDROME

 

Clinical: Overweight Orbital and ocular affectation progressive loss of visual acuity Intermittent caudication (has been present for 1 year) Cephaleea Cutaneous vasculitis Digital thrombosis (hallux) HTA HBP

Biological : Inflammatory syndrome pANCA 4,5 ui/ml Hb = 8,7g/dl C3 = 0,5 mg/l LA +++ Antibodies anti-β2GPI 34 EU/ml

 

 

• Solumedrol (1,5g/3 days) in recurrent pulses with evolution to remission of cutaneous vasculitis and orbitary inflammatory process.
• Cyclophosphamide
• Prednisone
• Vessel Due F
• Acenocumarol (Sintrom)
• Statine
• Coversion enzymes inhibitor
• Calcium channel blockers

Clinical progress under the treatment, but vision loss in OS.
September 2006 - Fig.11

 

 

• Complete thrombosis of distal abdominal aort with normal permeability  of  illiac arteries (possibly through colateral) - Fig.12
• Lack of vizualization on the inferior mezenteric artery
• Free ascitic in medium quantity
  

 

Evolution - Fig.13, Fig.14

• 2 years of positive progress clinical evaluation every 3 months
• Breathing intercurrence followed by violent abdominal pains after 4-6 days ->Hospitalized
• Mesenteric infarction (terminal aortic obstruction and inferior mesenteric artery) CT confirmed late surgery intervention
• Exitus

 

• In 1992 Wegener granulomatosis was diagnosed by under skin nodules biopsy and the pyocyaneus infection was decelated by maxillary punction.
• In 2006 Wegener is confirmed by ethmoidal biopsy, although c-ANCA is not present, but an infection is decelated again (ELISA IgM for Lysteria)
• In 2006 the presence of the antiphospholipid antibodies is decelated
• In 2008 after intercurrent infection the inferior mesenteric artery and terminal aorta thrombosis occurs resulting in catastrophic antiphospholipid syndrome and Exitus.
• Infection is a major contributor to morbidity and mortality in WG and often mimics a disease flare or manifests as atypical features caused by treatment-related immunosuppression. Providers should have a low threshold for treating suspicious symptoms with antibiotics. (7)

The infection represents the mutual trigger both for the increase of cANCA

and for the exacerbation of the thrombosis mechanism due to APLA,  leading finally to a catastrophic antiphospholipid syndrome.

 

The evolution pattern of the antiphospholipid antibodies leads to the catastrophic

systemic inflammatory syndrome, due to the second infection impossible

to controle two years  after.

• Could the infection be the trigger of the catastrophic evolution of the Wegener granulomatosis?!

• Is there any possibility that the human body should produce antiphospholipid antibodies to protect  vessels endothelium  against  any agressive infection ?!

In conclusion:

• Granulomatosis ……… pyocyaneus
• Orbital  inflammatory pseudotumor ……… Lysteria ……… APS
• Granulomatosis ……… SEPSIS ……… CAPS ……… DEATH

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[2] Piette JC, Cervera R, Levy RA, Nasonov EL, Triplett DA, Shoenfeld Y. The catastrophic antiphospholipid syndrome-Asherson's syndrome. Ann Med Interne Paris 2003;154:195-6. Medline]  

[3] Asherson RA, Shoenfeld Y. The role of infection in the pathogenesis of catastrophic antiphospholipid syndrome. Molecular mimicry? J Rheumatol 2000;27:12-4. Medline]

[4] Shoenfeld Y, Blank M, Cervera R, Font J, Raschi E, Meroni PL. Infectious origin of the antiphospholipid syndrome. Ann Rheum Dis 2006;65:2-6. Medline]

[5] Cervera R, Asherson RA, Acevedo ML, et al. Antiphospholipid syndrome associated with infections: clinical and microbiological characteristics of 100 patients. Ann Rheum Dis 2004;63:1312-7. Medline]

[6] Asherson RA, Espinosa G, Cervera R, et al. Disseminated intravascular coagulation in catastrophic antiphospholipid syndrome: clinical and haematological characteristics of 23 patients. Ann Rheum Dis 2005;64:943-6. Medline]

[7] Seo P. Wegener's granulomatosis: managing more than inflammation. Curr Opin Rheum. January 2008;20:10-16. [Medline]