Orbital Pseudotumor  with Wegener's  Granulomatosis Developing Antiphospholipid Syndrome

Authors: Tatiana Rosca, MD, PhD, * Cristina Tanaseanu, MD,PhD,** Codruţ Sarafoleanu, MD, PhD, *** Ana Tatiana Şerban, MD **** *Emergency Clinical Hospital St.Pantelimon , Neurosurgery Departmnet, Bucharest, Romania ** Emergency Clinical Hospital St.Pantelimon, Internal Medicine Department, Bucharest, Romania *** Clinical Hospital Sf.Maria, ENT Department, Bucharest, Romania ****Endocrinology Institute I.C. Parhon, Bucharest, Romania

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.

January 2006Patient M.F., 42 y.o., with: Left orbital panniculitis VA decreased in OS PAPILLARY STASIS OS Motility affected in OS

DIPLOPIA

History:

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 Wegener1993: 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? Poze picior

2006: aspect of left inflammatory orbital pseudotumor poze 4

2006: aspect of left inflammatory orbital pseudotumor poze 4

Invastigation:

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.

ENT Consultation – Prof. Dr. C. Sarafoleanu

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.

The 4th day after decompression surgery The 8th day after decompression surgery

Stage diagnosis: CLINICALLeft 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

Complete thrombosis of distal abdominal aort with

normal permeability of illiac arteries (possibly through colateral) Lack of vizualization on the inferior mezenteric artery

Free ascitic in medium quantity

Evolution 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

Discussion: 1.In 1992 Wegener granulomatosis was diagnosed by under skin nodules biopsy and the pyocyaneus infection was decelated by maxillary punction.2.In 2006 Wegener is confirmed by ethmoidal biopsy, although c-ANCA is not present, but an infection is decelated again (ELISA IgM for Lysteria)3.In 2006 the presence of the antiphospholipid antibodies is decelated4.In 2008 after intercurrent infection the inferior mesenteric artery and terminal aorta thrombosis occurs resulting in catastrophic antiphospholipid syndrome and Exitus. 5. 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)

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.

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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