CASE PRESENTATION

By

Rasha Ali Abdel-Noor

Lecturer of internal medicine

&Rheumatology.

Tanta University, Faculty of

Medicine.

HISTORY

Afemale patient named F.E.E aged 47 years

from Elmehalla Elkobra ,Gharbia,married

and has 3 offsprings ,housewife and has no

special habits.

Complaints:

Acute sever pain in the 4 limbs mainly

in the lower limbs 2 days before

admission(Decemper 2013).

HISTORY OF THE PRESENT ILLNESS

The condition has been started two days

before admission by acute onset of sever

pain in both lower limbs from toes till

knees extending to upper limbs and it was

associated by tingling and numbness

sensation it was not associated with fever

or any arthralgia or mucocutaneous rashes.

These symptoms occurred one week after

an attack of diarrhea for which she received

incomplete course of ciprofloxacine.

PAST HISTORY

No past history of diabetes or hypertension

or chronic disease of medical importance.

No history of drug use or drug allergy.

Family history:

Irrelevant

Social history:

Average socioeconomic status.

EXAMINATION

General appearance: The patient was fully conscious ,alert looks ill with no special facial expression with normal decubitus in bed and average body built.

Vital signs:

Pulse: absent radial , ulner and brachial pulsations in both upper limbs.

absent both dorsalis pedis, ant and posterior tibial arteries weak femoral pulsations.

Intact pulsations in both carotids about 80 b/m regular rhythm with average force and volume.

BP: undetected in 4 limbs.

RR: 20 c/m

Temp: 37 C

Head &neck:

Central trachea.

No enlarged thyroid gland.

No congested neck viens.

No lymphadenopathy.

Chest : bilateral equal air entry with normal vesicular breathing .

Heart: normal heart sounds ,no added sounds or murmer.

Abdomen: lax abdomen ,no organomegaly or ascites or bruit.

Extremities:

absent pulsations as described above.

Cold extremites ,poor capillary filling but with no colour changes or any skin lesions.

Musculoskeletal examination :

No joint swelling, tenderness or limitation

of movements

Neurological examination:

Motor power & deep reflexes were normal

Sensation : parathesia at 4 limbs

INVESTIGATIONS

Duplex study of 4 limbs:

Marked diffuse narrowing of arterial tree

of both lower limbs starting from external

iliac arteries with absent flow at both

anterior tibial and dorsalis pedis arteries

Marked diffuse narrowing of both brachial

arteries with absent flow in both radial

and ulner arteries.

Absent atherosclerotic changes.

Patent superfical and deep venous system.

INVESTIGATIONS

FBG:90mg /dl

BU: 70 mg/dl

SC: 1.1 mg /dl

CBC:

HB : 11 gm /dl

WBCs : 15000 /cmm

Platlets : 201,000/cmm

L.F.T:

Bilirubin : 1mg/l

SGPT: 76 u/l

SGOT: 93u/l

S. Albumin: 3.4 gm/l

S.globulin : 3.1

ESR: 45 1st hr ,65 2nd hr

CRP :-ve

Abd US : normal

ECG: Normal sinus rhythm.

Echo: Normal

Emperically and urgently we treated this

patient as a case of an acute & sever form

of a large vessel vasculitis ,so we started

Pulse steroid one gram /day for 3 days .

IV pentoxyfilline every 8 hours .

Prophylactic dose of LMw heparin.

Low dose asprine.

And preparing her for CT angiography and

other immunological assay.

CT ANGIOGRAPHY

Normal aortic arch ,descending thoracic

and abdominal aorta with diffuse

narrowing of both external iliac arteries

with absence of atherosclerotic changes

favor the diagnosis of peripheral

vasculitis.

RESPONSE

Marked improvement of her ischemic pain after the 2nd dose of pulse steroid ,but the pulsations still was undetected.

With completing her lab . Investigations:

RF : -ve

ANA: -ve

P&C (ANCA): -ve

Virology:

HCV antibodies –ve

HBsAg -ve

HIV antibodies : positive

SURPRISE

Our patient is an HIV patient since 16

years and she is already on HAART

1-Aluvia:lopnavir200 mg &50 ritonavir

2-Aurobindo:emtricitabine 200 mg and

tenofovir disoproxil fumerate 300 mg.

She and her family denied all this

history due to its social stigmata.

DILEMMA

Is this case is large vessel vasculitis

associated with HIV or it is actually

HIVrelated vasculitis????

What about its treatment???

Is it a mistake to start with pulse steroid???

How could we continue??????

HIV RELATED VASCULOPATHY

Since the beginning of the HIV era in the

early 1980s much has been written about

rheumatic and immunologic complications

observed in this patient population,

including the co-occurrence of systemic

vascular inflammatory diseases .

Calabrase L H: Vasculitis and infection with the human immunodeficiency

virus.Rheum Dis Clin North Am 1991; 17: 131-47

TYPES Category I refers primarily to vasculitides diagnosed

according to ACR classification schemes that have been

reported in the setting of HIV infection.

Category II refers to secondary forms of vasculitis (e.g.

where a precipitin or mechanism can be identified such

as a specific infection or drug induced hypersensitivity.

Category III describes those vascular disorders that

appear to be unique and for which strong consideration

should be given. FA L K RJ, A N D R A S S Y K e t al.: Nomenclature of systemic vasculitides.Proposal of an international

consensus conference.Arthritis Rheum 1994; 37: 187-92.

HU N D E R GG, A R E N D W P, B L O C H D A e tal.: The American College of Rheumatology

1990 criteria for the classification of vasculitis.Introduction. Arthritis Rheum 1990; 33:1065-7.

CATEGORY I PRIMARY VASCULITIS IN HIV

HIV has infected an estimated 75 million people worldwide over the past 25 years , it should not be surprising to find documented accounts of just about any form of vascular inflammatory disease reported on a chance association basis.

UNAIDS/WHO: AIDS epidemic update. December 2000: 1-28.

Miscellaneous disorders with vascular

inflammation as a feature reported in HIV

Cutaneous PAN

Behcet’s syndrome

Primary angiitis of the central nervous system

Erythema nodosum.

Rheumatic fever ,Erythema elivatinum

diutinum.

Degos disease

Angiocentric lymphoproliferative disorders

Coronary arteritis

Eaosinophilic vasculitis

Leukocytoclastic vasculitis with follicular

accentuation

PATHOGENESIS

The pathophysiology of these reported cases is

also unclear but may be due to direct or an

indirect role for HIV itself. by way of uncontrolled

immune activation with attendant cytokine

release , which characterizes the underlying

infection.

L.H. Calabrese Infection with the Human Immunodeficiency Virus type 1 and

vascular inflammatory disease Clin Exp Rheumatol 2004; 22 (Suppl. 36):S87-S93.

CATEGORY II SECONDERY VASCULITIS

Given the immunopathology of progressive

immunodeficiency and opportunistic infections. It

is well known that vasculitis may arise in the

course of virtually any type of infection

(i.e,bacterial, fungal, mycobacterial, viral

parasitic) and that such pathologic lesions may

come about by way of direct angio-invasion or via

aberrantly directed host-mediated immune

defenses.

Secondary forms of vasculitis.

Infectious arteritis.

Cytomegalovirus .

Pneumocytstis carinii .

Toxoplamosis .

Herpes zoster associated .

Hepatitis C associated .

Drug-induced vasculitis .

Vasculitis associated with antiretrovirals .

CATEGORY III VASCULAR INFLAMMATORY

DISORDER UNIQE TO HIV

(1) cerebral vasculopathy with aneursymal

dilatation in HIV infected children.

(2) large vessel disease in HIV infected

patients .

T V MULAUDZI Vasculopathy is a major feature of HIV disease. CME July 2009 Vol.27

Aneurysms This disease affects much younger patients The

median age is between 30 and 40 years. However, the

majority of patients infected with HIV are females and

the reason for the male preponderance of aneurysmal

disease is unknown.

The pathogenesis of the aneurysms is uncertain.

Histology shows obliterative endarteritis involving

the vasa vasora of the major vessels. These vessels

are surrounded by neutrophils, which in turn are

surrounded by a cuff of plasma cells, lymphocytes and

monocytes. This eventually leads to thrombotic

occlusion of the vasa vasora with transmural necrosis

of the vessel wall, probably due to ischaemia.

The common sites for the aneurysms are

the common carotid and the superficial

femoral artery .They can, however, be

found throughout the body, tend to be

multiple, and typically have a multi-

loculated appearance . Many are in fact

false aneurysms due to disruption of the

vessel wall at the point of transmural

necrosis.

OCCLUSIVE DISEASE HIV-associated arterial occlusive disease is recognised

as a specific clinical entity. As for aneurysmal disease,

young males with a median age of 30 - 40 years are

mainly affected; it is difficult to explain this male

preponderance.

The underlying cause of occlusive disease is thought to

be related to vasculitis. The histological findings are

similar to those found in HIV-associated aneurysmal

disease. It has been suggested that a hypercoagulable

state might be involved. There have been reported

findings of anti-phospholipid antibody syndrome,

deficiencies of free protein S, protein C and anti-

thrombin 3, but these have been sporadic reports.

Clinically most patients present with advanced

disease and critical ischaemia affecting the lower limb.

In most patients the disease is confined to one limb, for

reasons that are obscure. It is interesting to note that on

Duplex Doppler imaging there is what appears to be a

pathognomonic sign with hypoechoic spotting within the

arterial wall (string of pearls sign).

Mulaudzi TV, Robbs JV, Pillay W, et al. Thrombectomy in HIV related peripheral arterial thrombosis: a

preliminary report. Eur J Vasc Endovasc Surg 2005; 30(1): 102-106.

Nair R, Robbs JV, Chetty R, Naidoo NG, Woolgar J. Occlusive arterial disease in HIV-infected patients: a

preliminary report. Eur J Vasc Endovasc Surg 2000; 20: 353-357.

Botes K, Van Marle J. Surgical intervention for HIV-related vascular disease. Eur J Vasc Endovasc Surg 2007; 34: 390-396.

HIV& TAKAYASU

There is striking clinicopathologic overlap

withTakayasu's disease.

Features of similarity include :

the young age of the patients, presence of multiple

aneurysms, involvement of large vessels, arteritic

and postarteritic changes of the vasa vasora, a

temporal sequence of events (active and healing

stages), and the absence of an obvious causative

agent.

Differences from Takayasu's: disease are the predominance of males, the proliferation of slit-like vascular spaces in the adventitia,the pronounced leukocytoclastic vasculitis of the vasa vasora, the absence of prominent intimal proliferation and atherosclerosis, and the clustering of the cases that coincides with the HIV/AIDS epidemic. The overlap with Takayasu's disease is not surprising given its so called idiopathic etiopathogenesis and overlap with several arteritides. In other words, there is a chance association between H1Vand vasculitis. RUN JAN CHETTY, SIXTO BATITANG AND RAJ NAIR, Large Artery Vasculopathy in HIV-Positive Patients: Another Vasculitic Enigma HUM PATHOL 2000 31:374-379

TREATMENT

Therapy for HIV-associated vasculitis

remains controversial and problematic,

with the largest reported experience being

that of Guillevin and colleagues who

advocate a combination of glucocorticoids,

apheresis and antiviral therapy .

GISSELBRECHT M, COHEN P, LORTHOLARY O et al.: Human

immunodeficiency virus related vasculitis. Clinical presentation of and therapeutic

approach to eight cases. Ann Med Interne (Paris) 1998; 149: 398-405.

Standard treatment has been offered for aneurysms,

including prosthetic grafts, and relatively recently,

endovascular therapy has been performed with stent

occlusive disease

In 33 of 36 (71%) patients, salvage was attempted

comprising thrombectomy with or without thrombolysis;

bypass was attempted in the remaining three patients.

Of the 64 patients, who had chronic occlusive disease,

primary amputation was necessary in 30 (47%) while no

treatment was offered to nine (14%) who were deemed to

be pre terminal.

Twenty-one patients were offered bypass surgery, and

four an endovascular procedure

SO OUR DECISSION WAS:

To continue on 40 mg prednisolone

Oral pentoxyphylline

Low dose asprine

Follow up after two week:

She was very well no ischemic pain but only mild neuropathic pain for which pregabalin was prescribed.

Pulse was detected well in her RT radial ,ulner and brachial also her left dorsalis pedis and ant tibial.

Felt but weaker lt radial and ulner.

Still undetected in her RT dorsalis pedis.

NEW DOPPLER AFTER ONE MONTH

Patent venous and arterial system of both

upper and lower limbs with no plaques or

stenosis with only biphasic flow for follow

up.

So we started gradual withdrwal of

steroid dose 5mg every week till it

was completely stopped.

Patient is now on pregabalin only

and HAART.

Another doppler study was done

after steroid withdrwal and it

showed the same results.

CBC: ( 4-4-2014)

HB:12.6

Platlets:247,000

WBCs:5800

Immunophenotyping:

CD4 : 734 (38%) N(430-1600)

CD8 : 618 (32%) N(280-1100)

CD4/CD8 : 1.2 N(1.2-6.2)

Viral load: ??

DILEMMA

Is this case is large vessel vasculitis

associated with HIV or it is actually

HIVrelated vasculitis????

What about its treatment???

Is it a mistake to start with pulse steroid???

How could we continue??????

OUR CASE IS:

HIV RELATED LARGE VESSLE VASCULITIS

CATEGORY III