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a patient presenting with a GBS-like

illness due to a SLE vasculitic flare who

was subsequently found to be also a

case of acute intermittent porphyria.

Case Report and Discussion

A 35-yr old female, came to the

emergency medica l services with

complaints of weakness of all four

limbs, difficulty in swallowing and

hoarseness of voice since 15 days.

The weakness was acute in onset

involving the lower limbs followed by

upper limbs with difficulty in getting

up from squatting and lying down

position. The weakness progressed

rapidly over one week with complete

quadriparesis. There was difficulty in

buttoning of clothes and in rais ing arms

above her head. She also developed

tingling and numbness in the hands

and feet. Weakness progressed further

and her voice became hoarse and she

was unable to swallow. There was no

history of fever, loose motions, cough

or any recent vaccination prior to the

onset of weakness. There was no history

of backache, shooting pain, altered

Guillain Barr Syndrome, Systemic Lupus Erythematosus andAcute Intermittent Porphyria A Deadly Trio

Ankita D Patil1, Niteen D Karnik2, Milind Y Nadkar3, Vishal A Gupta4, Krithika Muralidhara5,

Suresh Passidhi1

sensorium, or any flexor spasms.

There were no similar complaints in

the past. Patient had a history of joint

pain with swelling, involving both

the wrist joints and elbow joints four

years ago for which she was evaluated

at a private hospital and diagnosed

to have granulomatous synovit is .

She was then put on antitubercularmedication for six months comprising

Isoniazid, Rifampicin, Pyrazinamide

and Ethambutol for 2 months (Intensive

phase) followed by Isoniazid and

Rifampicin for 4 months (Continuation

phase). The symptoms recurred a year

later and she underwent a synovectomy

with histopathology suggestive of

tuberculous synovitis and the synovial

t issue grew MDR-TB (Mult idrug

resistant M. tub ercu lo sis) in MGIT

(Mycobacterium growth indicator

tube). She was started on treatment

for MDR-TB comprising of InjectionKanamycin 500mg OD, Tab Ethionamide

250mg BD, Tab Pyrazinamide 1500

mg OD, Tab Ethambutol 800 mg OD

and Tab Cycloserine 250 mg BD. She

took this treatment for two years and

had completed it two months prior

to presentation. Patient was also a

known case of hypertension since five

years on Tab Amlodipine and also of

bronc hial asthm a on irregular rescue

therapy with inhaled bronchodilators.

She had recurrent oral ulcers and

dryness of mouth since three months

and her ANA (anti-nuclear antibody)

test done at a private hospital was

found to be positive with a titre of

1:120 (homogenous pattern). Her family

history was noncontributory.

At presentation, she had a pulse

rate of 108 beats/min, blood pressure

of 180/110 mm of Hg, respiratory rate

of 20 per min with a single breath

1Resident; 2Professor and In-charge MICU; 3Professor and In-charge Rheumatology Services, 4Assistant Professor, 5Critical Care

Fellow, Department of Medicine, Seth GS Medical College and KEM Hospital, Mumbai, Maharashtra

Received: 07.10.2015; Accepted: 12.10.2015

C A S E O F T H E M O N T H

Introduction

In 1 9 5 2 , W o l f r a m e t a l f i r s td e s c r i b e d a c a s e o f S y s t e m i cLupus Erythematosus (SLE) who

later on developed acute intermittentporphyria. 1A study from Mayo Clinic

comprising of 676 cases of porphyria,

which were followed up for a period of

20 years, showed that SLE was present

in 2.2%. 2 Coexistence of SLE with

porphyria has been documented by

Harris et al in Arch Internal Med way

back in 1966.3Haendchen et al reported

a case of lupus who developed bullous

lesions compatible with porphyria

cutanea tarda during treatment with

chloroquine.4 Filiotou et al reported

a case of acute intermittent porphyria

(AIP) with SLE in 2002.5Sensorimotorquadriparesis in a suspected case

of SLE could be due to a Guillain

Barr syndrome (GBS)-like illness,

mononeuritis multiplex presenting

as plexopathies, an anterior spinal

artery syndrome presenting as acute

transverse myelitis or hypokalemic

periodic paralysis related to a coexistent

Sjogrens syndrome with renal tubular

acidosis. Reviewing the literature,

GBS as an initial presentation of SLE

has been reported in a few cases with

prevalence of 0.6-1.7%.6 We describe

Abstract

Peripheral nervous system involvement occurs in 3-18% patients of systemic lupus

erythematosus (SLE) cases. American College of Rheumatology (ACR) includes

19 neuropsychiatric syndromes for diagnosis of SLE divided into neurological

syndromes of central, peripheral and autonomic nervous systems along with

the psychiatric syndromes. Sensorimotor quadriparesis in a suspected case of

SLE could be due to a Guillain Barr (GBS)-like illness, mononeuritis multiplexpresenting as plexopathies, an anterior spinal artery syndrome or it can present

like an acute transverse myelitis or hypokalemic periodic paralysis related

to Sjogrens syndrome with renal tubular acidosis. We here report a case of a

fulminant quadriparesis due to a SLE flare which subsequently was also found

to be a case of Acute I ntermittent Porphyria.

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Fig. 1: Foleys catheter showing pinkurine

count of 16 per minute. She was pale.

There was no rash, joint tenderness or

swelling, cyanosis, lymphadenopathy

or icterus. On central nervous system

examination she was alert, conscious

and oriented. She had bilateral lower

motor neuron type of facial weakness,

palatal weakness with poor gag reflex.

Neck flexor weakness was present.

Motor system examination revealed

distal wasting of bilateral lower limbs

with decreased tone in both the upper

and lower limbs. The power was grade

3/5 in the proximal and gr ade 2/5 in the

distal upper limb muscles and grade

zero in the lower limbs. Superficial

and deep tendon reflexes were absent.

Sensory system examination revealed

loss of touch, pain and temperaturesensations by 50% in glove and stocking

distribution over both upper and lower

limbs. The vibration and joint position

sense were preserved. Rest of the

systemic examination was normal.

She was admitted in the medical

i n t e n s i v e c a r e u n i t . A c l i n i c a l

diagnosis of Guillain Barr syndrome

(GBS) with bulbar involvement and

impending respiratory involvement

was made. The background history of

hypertension, bronchial asthma and

evidence of distal muscle wasting in

lower limbs (motor polyneuropathy)

necessitated considering differentials

o f m ic r o s c o p ic p o lya n gi i t i s a n d

eosinophilic granulomatosis withpolyangiitis (EGPA). She had incidental

ANA t i t re o f 1 :120 (homogenous

pattern) with oral ulcers and dry

mouth; a possibility of background

systemic lupus erythematosus (SLE)

with vasculitic flare producing GBS-like

illness was considered. Her two years

history of MDR tuberculosis treatment

which ended two months prior to

the current illness also brings in the

picture, a possibility of drug-induced

lupus.

Her investigations at presentationare shown in Table 1.

She had anemia with elevated

erythrocyte sedimentation rate (ESR)

and C Reactive protein (CRP) levels.

Tests for HBsAg, Anti-HCV and HIV-1

and 2 by ELISA were negative. Urine

for porphyrins (done as a part of a

routine workup for every case of GBS)

was negative. Her electromyogram and

nerve conduction study (EMG-NCS)

was suggestive of severe sensorimotor

a x o n a l p o l y r a d i c u l o n e u r o p a t h y

affecting both upper and lower limbs

suggestive of acute motor sensory axonalneuropathy (AMSAN) variant of GBS .

CSF study revealed proteins of 14 mg%,

sugars 60 mg% with 2 lymphocytes/

mm 3. The pat ient was s tarted on

intravenous immunoglobulins (IVIg)

with a dose of 0.4 gm/kg/day for 5

days. Her autoimmune workup was

sent. On the second day of admission,

she developed tachypnea and her

single breath count dropped to eight.

She was intubated and put on invasive

vent i la t ion with FiO2 ( fract ion of

inspired oxygen) requirement of 50%

and PEEP (positive end-expiratory

pressure) of 5 cm. The autoimmune

workup reports obtained a day later is

given in Table 2.

The ANA was now positive with

very high titres (1:2560), homogenous

p a t t er n w i t h a n t i - d s D N A b e in g

positive with titres of 1:160. C3 and

C4 levels were low. The 24-hrs urine

protein was 1 gm and her d irect

Coombs test was positive. A clinical

diagnosis of SLE flare with vasculitis

presenting as GBS-like illness was

made. Anti-histone antibodies were

negative ruling out drug-induced

lupus. The pANCA positivity with

titres of 1:160 in the present scenario

was considered as secondary to SLE.

Possibility of microscopic polyangiitis

was considered; however, with high

titres of ANA and dsDNA, low C3 and

C4, microscopic polyangiitis (MPA) was

less likely. Although patient had history

of asthma, there was no eosinophilia,

hence eosinophilic granulomatosis withpolyangiitis (EGPA) was unlikely.

Patient was started on Injection

Methylprednisolone (MPS) 1 gm for 5

days along with hydroxychloroquine

2 0 0 m g O D f o l l o w e d b y o r a l

prednisolone 1 mg/kg/day. Patients

power improved over the next seven

days to grade 4 in the upper limbs

and grade 2 in the lower limbs and

the process of weaning from ventilator

was initiated. Her urine was noticed

to be persistently pink (Figure 1). A

repeat urine test for porphobilinogen

sent on day five at our hospital was

negative. However on day eleven of her

admission, we repeated the complete

panel for screening and confirmatory

tests for porphyria. The results are

given in Table 3.

UV fluorescence was used as a

screening test but it detects only

uroporphyrins and coproporphyrins

but not porphobilinogen (PBG). This

test was negative in our case on two

occasions. Hoeschs test (screening test)

is performed with Ehrlichs reagent

which gives a cherry-red colour whenmixed with PBG containing urine.

Watson Schwartz test (confirmatory

test) is performed only if Hoeschs test

samples are positive and uses saturated

sodium acetate solution along with

chloroform and butanol in addition to

Ehrlichs reagent used in Hoeschs test.7

This brought into the differential

d ia gn o s is a p o s s ib i l i t y o f a c ut e

intermittent porphyria presenting

w i t h G B S - l i k e i l l n e s s . S h e w a s

kept euglycemic (on ora l glucose

and intravenous dextrose). Injection

Table 1: Investigations at presentation

Hb 8.4 gm/dl

TLC 5800/mm3

Dierential count N77 L21 M02 E00

Platelets 2 lakhs/mm3

BUN 14.0 mg/dl

Serum creatinine 1.2 mg/dlSerum sodium 140 mmol/l

Serum potassium 3.6 mmol/l

Random blood sugar 96 mg/dl

Total protein 5.8 gm/dl

Serum albumin 2.4 gm/dl

SGOT 15 IU/l

SGPT 5 IU/l

ESR 90 mm/hr

CRP levels 120 mg/dl (N: 0 -10mg/dl)

Urine routineexamination

2+ protein, largenumber of RBCs

Table 2: Autoimmune workup

ANA Positive, homogenouspaern, 1:2560

Anti-dsDNA Positive with 1:160 titres

Anti-histone antibodies Negative

C3 Low 37 mg% (N 80-180)

C4 Low 5 mg% (N 10-40)

pANCA Positive with 1:160 titres

Direct Coombs test Positive

24-hrs urine protein 1 gm

Table 3: Tests for Urine Porphyria

UV uorescence (screening test) Negative

Hoeschs test (screening test) Positive

Watson Schwar (conrmatory test) Positive

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Hematin is not available in India;

hence was not given. Amlodipine and

Hydroxychloroquine were stopped in

view of porphyrogenic potential. Care

was taken to avoid porphyrogenic

drugs. Patient could be weaned off the

ventilator by Day 15.

She had responded to the treatment

( IVIg, In j . MPS fo l lowed by ora l

p r e d n i s o l o n e ) a n d h e n c e c o u l d

be we aned of f the ve nti lator with

improving power in both the upper

and lower limbs. She was switchedto metal tracheostomy tube by Day

30. Her antihypertensive medications

were changed to Tab. Telmisartan.

Metoprolol and clonidine were given

to control her autonomic disturbances.

Over the next month, her power in the

lower limbs persisted to be grade 2,

she had general debility and attempts

to close the metal tracheostomy tube

were unsuccessful. In view of her

general condition, kidney biopsy was

deferred. She developed a left lower

lobe consolidation on Day 45 and

grew Acinetobacter species which was

sensitive only to Colistin. We were

compelled to start Colistin (safety

profile for porphyria unknown). She

eventually required ventilator support

and developed autonomic disturbances

in the form of tachyarrhythmias and

had an episode of cardiac arrest needing

cardiopulmonary resuscitation. This

was followed by sepsis and acute

oligoanuric renal failure to which she

succumbed on Day 60 of MICU stay.

Thus, our patient presented with

fulminant quadriparesis with bulbar

and respiratory muscle involvement.

H e r n e r v e c o n d u c t i o n s t u d i e s

supported a diagnosis of AMSAN.

Seventy percent of GBS cases have

a preceeding history of an upper

respiratory infection or gastroenteritis

(et io logies - Campylobacter je juni,

human herpes virus, and Mycoplasma

pneum oni a) or recent immunizations,

which she lacked.

An ANA positivity of 1:2560 with

Anti-dsDNA positivity of 1:160 with

low levels of C3 and C4 clinched the

diagnosis of SLE with vasculitic flare

presenting as a GBS-like illness. An

ANA positivity after two and half

years of antitubercular treatment (6

months of Category I and two years

of MDR tuberculosis regimen) brings

a differential of drug-induced lupus.The differences between SLE and drug-

induced lupus are outlined in Table 4.

Drug-induced lupus is seen in older

age group and usually is associated

only with skin manifestations; central

nervous system and renal involvement

are very rare. A kidney biopsy would

have been helpful to differentiate

lupus nephritis from renal involvement

of MPA which would have been

pauciimmune in nature.

P e r i p h e r a l n e r v o u s s y s t e m

involvement occurs in 3-18% patientsof Systemic Lupus Erythematosus.8

GBS is classified under the peripheral

n er v e in v o lv em en t b ut i s r a r e ly

reported. Okoh HC et al have reported

a case of SLE presenting as a Miller

Fischer variant of GBS as the primary

manifestation of SLE in 2015 in Jamaica. 8

Laarhoven et al reported a case of GBS

as a presenting feature in a patient with

lupus nephritis.6

AIP is known to present with

a G B S - l i k e i l l n e s s a l o n g w i t h

autonomic dysfunction, abdominal

pain, convulsions, tachycardia and

h y p e r t e n s i o n . T h e n e u r o l o g i c a l

presentation comprises of symmetrical

muscle weakness with aref lex ia ,

sensory symptoms in the form of

paresthesias and tingling numbness in

the glove stocking regions along with

cranial neuropathies.9UV fluorescence

used as a screening test, was negative

on two occasions. This test detects only

uroporphyrins and coproporphyrins

but not porp hobi linogen (PBG). The

Hoeschs test and the confirmatory

Watson Schwartz test clinched the

diagnosis of porphyria in our patient.

What precipitated porphyria in this

case is debatable. She was on amlodipine

for five years and had received two and

half years of antitubercular therapy.

She was put on hydroxychloroquine

on diagnosis of SLE. All these arepotentially porphyrogenic drugs.10

The most common drugs precipitating

porphyria are listed in Table 5.

Does an association really exist

b e t ween p or p h yri a a nd SLE ? T o

investigate this association, Allard

et al investigated 38 patients with

various types of porphyrias for clinical

evidence of a connective tissue disease.11

Antinuclear antibodies (ANAs) were

found in 53% (8/15) patients with acute

intermittent porphyria. These patients

were more likely to have had a recent

acute attack of porphyria. Antinuclear

antibodies were not found in any

patients with any of the other types of

porphyria. Haendchen et al reported a

case of lupus who developed bullous

lesions compatible with porphyria

cutanea tarda during treatment with

chloroquine.4

The reasons o f the associa t ion

b e t wee n SL E a n d p or p h yr i a a r e

unknown. Harr is and co l leagues

proposed that porphyria can trigger

an immune response favouring SLE. 3

The accumulat ion of porphyrins

Table 4: SLE vs drug-induced SLE

Features SLE Drug-inducedlupus

Clinical

Age of onset 20-30 yrs 50-70 yrs

Gender F:M::9:1 F:M::1:1

Ethnic ity Blacks > whites Whites > blacks

Systemsinvolved

Frequentlyinvolveskidney or CNS

Rarely involves

Skinmanifestations

In >75% cases 25% only

Raynaudsphenomenon

In >95% cases 25% only

Course Indolent Limited*

Laboratory

Anti-histoneantibodies

High in 50%cases

>95%

Anti-dsDNAantibodies

High in 80%cases

Rarely high

C3 and C4 Decreased Normal

*Usually resolves over several weeks after

discontinuation of the oending medication

Table 5: Common unsafe drugs in porphyria

Porphyrogenic drugs

Documented Probable Possible

Clindamycin Amlodipine Hydroxychloroquine Escitalopram

Nitrofurantoin Atorvastatin Indomethacin Multivitamins

Phenytoin Ceftriaxone Prednisolone Glimepiride

Rifampicin Zidovudine Linezolid GlipizideIsoniazid Diazepam Clopidogrel

Cotrimoxazole Diclofenac Methlyprednisolone

Spironolactone Diltiazem Cyclophosphamide

Valproic acid Tetracyclines Metronidazole

Fluconazole Midazolam

Tramadol Telmisartan

Voriconazole Doxycycline

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causes activation of the complement

system and increases neutrophil

chemotaxis when there is exposure

to ultraviolet rays. Porphyrins can

also cause tissue damage leading to

release of autoantigens that serve as

a source for antibody formation. Pre-

existing lupus can result in an acquired

metabolic fault leading to porphyria,

and lupus precipitating a genetically

determined metabolic fault can result

in porphyria.12 An interesting fact is

that both SLE and porphyrias have

a predisposing genetic component

situated on the same chromosome.

The gene for the decarboxylase of

the uroporphyrinogen (UROD), the

enzyme deficient in cases of porphyria

cutanea tarda (PCT) is located on

chromosome 1 (1p34) and the region

1q41-1q42 has been associated withSLE. Hence, although uncommon the

association between porphyria and

lupus deserves attention.

In our case, it could be postulated

that one or more of the drugs that

the patient was exposed to prior to

her acute presentation could have

resulted in accumulation of porphyrins.

These could have produced tissue

damage leading to release of auto

ant igens . The genet ic associa t ion

outlined above could have resulted

in these autoantigens precipitating a

GBS-like illness as a manifestation of a

fulminant SLE flare.

Conclusion

Guillain Barr syndrome (GBS) can

be a pr ese nt at io n of bo th sy st em ic

lup us er y t h em a t o s us ( SL E ) a n d

acute intermittent porphyria (AIP).

This case highl ights a very rare

association between porphyria and

SLE and underlines the importance

o f r ec o gn is in g t h e c o n f o un d in g

presentations especially in females of

child-bearing age.

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