PRESENTATION OF BEHCET”S DISEASE AMONG NIGERIANS

Word count: Abstract 232, body 1652 Table count: 6 Figure count: 5

1. Dr F.O.A Ajose,

Dermatology Unit, Lagos State University Teaching Hospital, Ikeja. Lagos

2. Prof O.O. Adelowo,

Rheumatology Unit, Lagos State University Teaching Hospital, Ikeja. Lagos

3. Dr O. Oderinlo

Eye Foundation Hospital, Ikeja. Lagos

Correspondence:

Dr Frances O. A. Ajose FRCP(Lond)

PO Box 1723. Surulere, Lagos. Nigeria

Email- francesajose@yahoo.co.uk

Funding: self

Conflict of Interest: Nil

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ABSTRACT

Background: Behcet’s Disease (BD) is a chronic multisystemic inflammatory pan-vasculitis of

unknown aetiology, which commonly involves the skin, joints, eyes, mucosa, central nervous

system and gastrointestinal tract.

It is considered to be due to an auto immune reaction triggered by a yet to be identified infectious

agent in a genetically predisposed person. It most commonly affects persons of Mediterranean

and Far Eastern origin and is considered to be rare among black Africans.

Objective: To document the clinical pattern of Nigerian patients presenting with Behcet’s

disease at a tertiary hospital in Nigeria.

Method: A retrospective study of patients who attended dermatology and rheumatology clinics

of Lagos State University Teaching Hospital, Ikeja, Nigeria between August 2007 and August

2011 and who fulfilled the ISG diagnostic criteria for Behcet's Disease. Patients were referred

from hospital specialists that included ophthalmologists, dentists, psychiatrists and

otorhinolaryngologists.

Result: Fifteen patients, (female 11, male 4) aged between 22-50years, were diagnosed with

BD. Onset was mostly in the second decade but diagnosis was made at a mean age of

33years.Mucosal BD was predominant at80%,with mixed mucosal and ocular pattern in 60%,

and mixed mucosal and neuro Behcet's in 13%. Articular involvement was present in 87%.

Management was with standard immunosuppressive agents.

Conclusion: BD though rare, is seen among Nigerians and its presentation is not much different

from reports elsewhere.

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Key words: Behcet's Disease, Uveitis, Arthritis, Genital ulcers, Erythema Nodosum, Nigerians

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INTRODUCTION

Behcet’s disease (BD) also often called Behcet’s syndrome, because of the uncertainty of its

pathogenesis and lack of diagnostic tests, is a chronic auto inflammatory disorder of unknown

aetiology. It is considered to be an auto immune condition triggered by a yet to be identified

infectious agent in a genetically predisposed person and under certain environment.1,2 The disease

has been reported worldwide, though it is mostly seen in persons along the old ‘silk route’ of

eastern Mediterranean, Middle East and East Asia. The condition is also more severe in these

areas.3 Turkey probably has the highest occurrence of the disease with a prevalence of between

110 - 420 per 100, 000 population, 2, 3 while in Japan it is seen in 13–20 per 100,000 population.

It has been infrequently reported in Northern Europe, Africa and the Americas.4 All ages are

affected. Frequency is, however, higher in persons in their third or fourth decade of life, with a

mean of 25 – 30 years. Sex predominance is also variable in different geographical areas. Thus,

while the female to male frequency is identical in patients along the ‘silk route’, there is a female

preponderance in Japan, Korea and the western countries.3, 4

The clinical manifestations are protean and these have been attributed to an underlying vasculitis

that may involve an artery or vein in any organ.5 Behcet’s disease however mostly affects the

skin, eyes, mucous membranes and the central nervous system. Other systems such as the

musculo-skeletal, gastro-intestinal and genito-urinary may however also be involved.

There have been few reports from Africa and these are among North African Tunisians and

Egyptians.6, 7 but very few cases have been reported among Sub-Saharan Africans.8, 9 There are,

however, case reports among black Africans resident in United Kingdom.10 There have been no

documented reports of BD among Nigerians and other West Africans.

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The objective of this study therefore is to document the clinical presentation of Behcet’s disease

among Nigerians and compare their presentations with reports elsewhere.

PATIENTS AND METHODS

This is a retrospective study of patients with BD who presented to the dermatology and

rheumatology clinics of Lagos State University Teaching Hospital, Ikeja between 2007and

2011.The hospital is located in Lagos, the commercial capital and most populous state in Nigeria

and receives patients from all over the country. The study patients fulfilled the criteria of the

International Study Group (ISG) on Behcet’s Disease which included recurrent oral ulcers,

recurrent genital ulcers, eye lesions, skin lesions and pathergy.11 Table 1 shows sources of

referral of the BD patients. All patients had complete blood count, erythrocyte sedimentation

rate, and in some patients serology that included antinuclear antibody, rheumatoid factor, HIV

and syphilis diagnostic tests. Treatment was essentially with the standard drugs used in BD,

including corticosteroids and Disease Modifying Anti- rheumatic Drugs.

RESULTS

A total of 15 Nigerians fulfilled the ISG criteria for Behcet’s Disease over the four year study

period. All but four of the patients presented as undiagnosed referrals from various departments

in the hospital (Table 1). The demographic characteristics of the patients are as in Table 2.

Females were predominant. The mean age at presentation was 33.3 years (range 22-40). The

commonest presentation was mouth ulcers (Table 3) with the tongue being the commonest site.

Fig 1 shows ulcer on the tongue of one of the patients. Episodes of painful ulceration were

without fevers or regional lymphadenopathy. The scrotum in males (Fig 2) and labia in females

were the commonest sites of genital ulceration. Dyspareunia was significant complaint in two

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females and in one of the male patients, scrotal ulceration was severe enough to mimic

Fournier’s gangrene. Tests for HIV, syphilis and chlamydia were negative in all the 11patients so

tested.

Erythema nodosum was the commonest skin involvement, being seen in 9 cases. Other skin

involvement included pseudo-folliculitis (Fig.3), pustules at injection sites, superficial

thrombophlebitis and hair structure changes. Table 3 highlights the frequency of the skin

changes.

Eye involvement was seen in 12 out of our 15 patients. The ocular involvement was preceded by

oral and genital ulcers in all the cases. Eye involvement was bilateral in all cases with anterior

uveitis in 5 patients (Table 3) and transient hairline hypopyon in one patient. Posterior uveitis

was seen in 4 patients and pan- uveitis with severe retinal damage in 2 cases (Fig 4&5). Ultra

sound scanning of the retina in one of these patients (Figs 6 & 7) shows extensive vitritis and

posterior vitreous detachment.

Arthritis was present in 87% (13/15) with a total of 19 joints involvement (Table 3). The knee

was the commonest joint involved and most patients had more than one joint involvement.

Anxiety and depression were the commonest manifestation of Central Nervous System (CNS)

involvement (Table5), present in 9 out of 15 patients. Other CNS involvement included

sensorineural deafness in 3 patients. One patient had transient facial nerve palsy, hemiparesis and

seizures and another patient presented with psychomotor hyperactivity and cognitive

impairment.

Laboratory results were as in Table 6 with most of the patients having elevated erythrocyte

sedimentation rate. Serology for ANA, syphilis were negative in all tested. Treatment was

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mostly with corticosteroids and immunosuppressives. Twelve patients received corticosteroids

with or without immunosuppressives. Three patients had methotrexate or azathioprine, in

addition to corticosteroids. Two patients received colchicine and another, cyclosporine, for

variable periods.

DISCUSSION

Although worldwide in distribution, Behcet’s disease has rarely been reported among Sub-

Saharan Africans. Probably the largest documented case series was by Jacyk8 who reported 5

cases from South Africa. Nunzi et al9 reported a case from Congo. Another report from

Comoros12 involved 14 cases. In a report of Behcet’s disease patients of West African and Afro-

Caribbean origin living in London, United Kingdom, Poon et al10 confirmed the rarity of this

disease. He suggested environmental factors, absent in the patients’ home country, as

contributing to the disease presumably because no previous report of BD had come from West

Africa. The eight patients in the report of Poon et al had lived in the United Kingdom for a

number of years. Although, all the six patients tested were negative for HLA B 51, they

nevertheless concluded that their clinical progress was similar to European patients. This view

was supported by the finding of refractory ocular inflammation that responded poorly to

immunosuppressives.

The mean age of onset in our patients was 27.3 while mean age at presentation was 33 years in

consonance with the commonly reported age range of 25 – 30 years elsewhere.13 There was

therefore an average delay of six years before appropriate diagnosis was made. While females

and males are reported in equal proportions in most studies, our cohort had a marked female

preponderance of 11 to 4. In sharp contrast to the male preponderance in the study from the

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Comoros (F-4: M-10). The reason for this female preponderance is unclear as it cannot be

explained by the slight female preponderance in our hospital patient attendance.

As in the other studies, oral and genital ulcers were the commonest presentation in our cohort.

Twelve (80%) had eye involvement unlike the 50% reported by Evereklioglu.14 Although

transient hypopyon is often thought to be the hallmark of ocular presentation in BD5 and Tugal-

Tutkum et al. reported this in 12% of their series,15 only one of our patients had hypopyon.

Furthermore, anterior / posterior uveitis rather than pan uveitis was predominant among our

patients.

Arabaci et al 16 and Direskeneli17 found poor dental hygiene in their cohort, but our patients’

hygiene indices were fair to good. This difference may be due to the fact that most of our

patients used local chewing stick which is better tolerated than the standard toothbrush in periods

of oral ulceration.

The commonest skin manifestation among our patients was erythema nodosum which was seen

in nine out of our 15 cases (60%). Erythema nodosum has previously been reported in 50% of

patients with BD.18 The change in hair structure to a silky texture was observed in two patients.

This strange regression of African hair to the neonatal hair structure had been reported in other

chronic diseases including HIV and Rheumatoid arthritis.19

Arthritis was seen in 80% of our patients who had a total of 19 joint involvements. As reported

elsewhere, oligo - articular presentation was most frequent and the knee and ankle, the

commonest sites.

8

CNS involvement was present in 12 patients in our study. Unlike the findings of Borhani et al20

depression rather than somatisation was the significant psycho morbidity, although we used a

different instrument. However we did not find symptoms attributable to somatization in our

patients. Hemiparesis and transient facial nerve palsy were observed in one patient each.

Cerebrospinal fluid examination and imaging studies were however not done.

Treatment was mostly with corticosteroids and/or immunosuppressives and choice was

dependent on availability of these medications.

The limitation of this study was that HLA B51 which characterizes Behcet’s Disease was not

available to us. However studies of the global distribution of HLAB51 had indicated its rarity

among Sub Saharan Africans.9 This was supported by the study from the Comoros13 which

reported this allele negative among east African BD patients. Nevertheless it would be useful to

know that this is so in our population. Another limitation was default rate among the patients

which made assessment of the efficacy of the drugs used difficult. The rather long onset to

diagnosis period of six years may indicate a poor ascertainment of the disease among relevant

clinicians in Nigeria which should be addressed. With improved ascertainment, it is hoped that

more cases will be diagnosed and a larger prospective study may then elucidate this condition

further

CONCLUSION

Behcet’s disease is here reported for the first time among 15 Nigerians. Whilst the number is

small, the presentation may reflect the rarity of BD in the Nigerian population or poor

ascertainment of the disease among relevant clinicians. It is hoped that this study will increase

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the awareness of this condition among clinicians attending to African patients in Africa and

elsewhere.

REFERENCES

1. Onder M, Gurer MA. The multiple faces of Behçet’s disease and its aetiological factors. J Eur

Acad Dermatol Venereol 2001; 15:126–36.

2. Direskeneli H. Behcet’s disease: Infectious etiology, new auto antigens, and HLA-B51 Ann.

Rheum Dis. 2001: 60: 996-1002

3. Zouboulis C. C. Epidemiology of Adamantiades – Behcet’s disease. In: Zierhut M, Ohno S, eds.

Immunology of Behcet’s Disease. Amsterdam: Grafischm Produktiebedrijf Gorter 2003: 1-16

4. Zouboulis C C, Kotler I, Diawarr D, et al. Adamantiades – Behcet’s disease: epidemiology in

Germany and in Europe. In: Lee S, Bang D, Lee ES, Lee S, Eds. In Behcet’s disease A guide to its

clinical understanding. Textbook and Atlas. Springer 2001; 157 – 69

5. Schirmer M, Calamia K T. Is there a place for large vessel disease in the diagnostic criteria for

Behcet’s disease? J Rheumatol. 1999; 26: 2511-2

6. Houman MH, Neffati H, Braham A et al Behcet’s disease in Tunisia. Demographic, clinical and

genetic aspects in 260 patients. Clin. Exp. Rheumatol 2007. Jul-Aug; 25 (4 suppl 45):558-64

7. El Menyawi MM, Raslan HM, Edrees A. Clinical features of Behcet’s disease in Egypt Rheumatol

Int 2009 Apr; 29 (6): 641-6

8. Jacyk WK. Behcet’s disease in South African Blacks: report of five cases

J Am Acad Dermatol 1994 May; 30(5 Pt 2): 869 -73

9. Nunzi E, Clapasson A, Di Negro G, Noto S. A case of ‘silk route disease’ in a patient from Congo.

G G.Ital..Dermatol Venereol 2008 Jun; 143(3): 225-6

10. Poon W, Verity DH, Larkin GL, Graham EM, Stanford MR. Behcet’s disease in patients of west

African and Afro-Caribbean origin. Br J Ophthalmol 2003;87:876-878

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11. International Study Group for Behcet’s Disease: Criteria for diagnosis of Behcet’s disease.

International study Group for Behcet’s Disease. Lancet 1990;335:1078-80

12. Liozon E, Roussin C, Puechal X et al. Behcet’s disease in East African Patients may not be

unusual and is an HLA B51 negative condition: A case series from Mayotte (Comoros). Joint

Bone Spine 2010 July 2 [Epub ahead of print]

13. H. Yazici, Y. Tuzun, H. Pazarli, S. Yurdakul et al. Influence of age of onset and patient's sex on

the prevalence and severity of manifestations of Behcet's syndrome. Ann. Rheum Dis, 1984, 43,

783-789

14. Evereklioglu C. Current concepts in the etiology and treatment of Behcet’s disease. Surv.

Ophthalmol 2005;50(4): 297-350

15. Tutkum I, Onal S, Altan-Yaycioglu R et al Uveitis in Behcet’s disease: an analysis of 880 patients.

Am J Ophthalmol 2004;138(3): 373-380

16. Arabaci T, Kara C, CiçekY. Relationship between periodontal parameters and Behcet's

disease and evaluation of different treatments for oral recurrent aphthous stomatitis. J

Periodontal Res. 2009 Dec;44(6):718-25. Epub 2008 Dec 11.

17. Direskeneli H, Mumcu G. A possible decline in the incidence and severity of Behcet's

disease: implications for an infectious etiology and oral health. Clin Exp Rheumatol. 2010

Jul-Aug;28(4 Suppl 60):S86-90. Epub 2010 Sep 24.

18. Yazici H, Fresco I, Stuebiger N. Behcet’s syndrome, relapsing polychondritis, and eye

involvement in rheumatic disease In: Bijlsmaed Eular Compendium on Rheumatic Diseases BMJ

Publishing Group 2009:357-374

19. Ajose, F. O. A. (2012), Diseases that turn African hair silky. International Journal of Dermatology,

51: 12–16. doi: 10.1111/j.1365-4632.2012.05556.x

20. A. Borhani Haghighi, E. Aflaki1, H. Haghshenas2, et al. Psychometric evaluation of patients with

Behçet's disease Iran J. Med Sc. June 2007; Vol 32 No 2

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Ophthalmology 4

Self- referral 4

Otorhinolaryngology 2

Gynecology 2

Urology 2

Psychiatry 1

Table 1.Sources of referrals of Behcet's Disease patients in Nigeria

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Total number of

Subjects

- Female (%)

- Male (%)

15

11(73.3)

4(26.7)

Age range 16-40

Mean 32.9

Table 2: Demography of Behcet's Disease patients in Nigeria

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1. Mouth ulcers 15

2. Genital ulcersScrotalVulvaPerineal

14392

3. ArthritisAnkleKneeWristElbow

128911

4. Skin InvolvementErythema nodosumPseudofolliculitisThrombophlebitisPustules at injection sitesHair Structure changes

12973

5

25. Eye Involvement

Anterior UveitisPosterior UveitisPan Uveitis Transient hairline hypopyon.

95421

Table 3: Clinical presentations in Behcet's Disease patients in Nigeria

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Depression 9

Anxiety 4

Cognitive symptoms 1

Sensorineural deafness 1

Hallucinations, Delusions 1

Hemiparesis 1

Facial Nerve Palsy 1

Chorea 1

Seizures

1

Table 4: Neuro-psychiatric presentations of Behcet's Disease patients in Nigeria

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Haematocrit:

Range

Mean

29-45 %

36 %

ESR:

Range

Mean

21-150mm/hr

72.8mm/hr

Serology:

ANA

Retrovirus

Syphilis

8 negative (7 not done)

12 negative (5 not done)

11 done (all negative)

Table 5: Laboratory Investigations of Behcet's Disease patients in Nigeria

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Corticosteroids, Prednisolone/ Pulse

Methylprednisolone

12

Azathioprine 3

Methotrexate 3

Cyclosporin 1

Colchicine 2

Table 6: Treatment of subjects withBehcet's Disease in Nigeria

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Fig 1. Ulcers on the tongue of 34 year old male Nigerian with Behcet’s Disease

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Fig 2 showing penile ulcers in a Nigerian with Behcet's Disease

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Fig. 3 Pseudo-folliculitis in a Nigerian with Behcet’s Disease.

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Fig 4. Photograph of the eye showing cataract formation and extensive posterior synechae following

recurrent uveitis in a Nigerian with Behcet's disease.

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Fig 5. Photograph of the eye of a Nigerian with Behcet's disease showing extensive vascular

sheathing and retinal pigment attenuation as well as well as epithelial atrophy and macula hole

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Fig 5. Ultrasound scan of the eyes showing extensive vitritis with posterior vitreous

detachment and vitreo-retinal traction in a Nigerian with Behcet’s Disease.

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