Behavioral and Cognitive Impairments as Presenting Features of Behçet's Disease

To the Editor: Behçet's disease (BD) is an inflammatory disease of unknown etiology characterized by relapsing episodes of oral aphthous ulcers, genital ulcers, uveitis, and skin lesions. Other systems, including vascular, gastrointestinal, and CNS can also be involved. It is most commonly seen in the Mediterranean, Middle East, and Far East regions.^1,2 The diagnosis is clinical, based on International Study Group (ISG) of Behçet's Disease criteria.³ It is rare in the United States, with prevalence rates estimated to be 0.12 to 0.33 per 100,000.¹ Various studies have found neurological involvement in 1.3% to 59% of cases.^4–7 Two main categories of CNS involvement are described: parenchymal, which mostly manifests as subacute meningoencephalitis; and nonparenchymal, which mainly involves the cerebral vascular structures. Cognitive and behavioral symptoms can occur with or without overt CNS involvement.^8–10 We present a case of diagnosis of BD in a patient who initially presented to psychiatric care with neuropsychiatric symptoms without significant neurological signs or symptoms.

Case Report

A 39-year-old African American man was admitted to the inpatient psychiatric unit because of agitation, disinhibited behaviors, and decline in functioning resulting in inability to take care of his basic activities. According to his family, about 2 years before this hospitalization, he was found lying in the street, his head apparently swollen. Before that incident, he was functioning normally; he worked in his family business and paid a lot of attention to his grooming. After that incident, he became neglectful of his hygiene, was disruptive at home and in the neighborhood, became threatening toward his family members, and was forgetful. Family members also noticed slurring of his speech. He resisted the family's attempts to get him medical attention. Eventually, he ended up living in an abandoned building in extremely unsanitary conditions. He stole from his neighbors and tore off and sold the siding from the house. On admission, remarkable mental status examination findings were poor hygiene; loud, slightly dysarthric speech; irritable and labile affect; and poverty of thought content. No psychotic symptoms were elicited. A Mini-Mental State Exam showed deficits in orientation and short-term recall. He was uncooperative with further neuropsychological evaluation. He did not have any focal neurological signs. A CT scan of his brain showed mildly increased cortical sulci. He was referred to a neurologist, and differential diagnoses of postconcussive behavioral changes and vascular dementia secondary to a stroke were considered, and aspirin 81 mg was started. During his hospital stay, he also developed two ulcers in his scrotum and folliculitis in thigh and scrotum which responded to symptomatic treatment. A work-up for sexually transmitted diseases, including Herpes Simplex Virus (HSV) was negative. He had poor dental hygiene and underwent dental extractions. He also had monoarticular arthritis of his right knee. X-ray of his knee was normal, and the inflammation resolved after brief treatment with NSAIDs. His behavioral problems were treated symptomatically with valproic acid 1,500 mg and citalopram 10 mg, which were partially effective. He was subsequently discharged to his family's care with follow-up arrangements with a neurologist and a psychiatrist.

About 1 year later, the patient was readmitted to the inpatient unit. He had been living in an abandoned house where he accidentally started a fire; he had lit a grill on the porch and, after some time, he left the house having forgotten all about the grill. According to his family, after his previous hospitalization, he lived with the family for a short period but then left the house and started living in the abandoned house again. An MRI of brain that had been done after his first hospitalization showed T2 hyperintensities in left basal ganglia, thalamus, and cerebral peduncle that were considered to be “suggestive of proximal propagation of Wallerian degeneration likely associated with a pontine infarct.” Diffuse cortical atrophy was also noted. On exam, his mental status and cognitive function were quite similar to his previous hospitalization. No focal neurological signs were present. During this hospitalization, a whitish coating of his tongue was noted, and he was treated for oral candidiasis. On further exam, oral ulcers were also noted. He also appeared to be walking awkwardly and was found to have multiple genital ulcers. He also developed right knee swelling during the hospitalization. Based on the constellation of symptoms over the two hospitalizations, an underlying systemic illness was suspected. Laboratory testing showed elevated erythrocyte sedimentation rate (72 mm/hr.) and C-reactive protein (34.1 mg/L). He was then referred to a rheumatologist, and a clinical diagnosis of BD was made. Further testing showed that ANA (antinuclear antibody), ENA (extractable-nuclear antibody), and rheumatoid factor were negative. Anti-Cardiolipin IgM and IgG, and C3 and C4 complement were normal. Lupus anticoagulant was positive. HSV Type 1 IgG was positive, but HIV, VDRL, and HSV Type 2 IgG were negative. Pathergy test was negative. His behavioral symptoms were stabilized partially on valproic acid and citalopram. He was subsequently discharged to a supervised group home and started immunosuppressive therapy with the rheumatologist. He was also scheduled for follow-up appointments with a neurologist and a psychiatrist.

Discussion

BD is considered rare in the United States. According to the diagnostic criteria recommended by the ISG for Behçet's Disease, recurrent oral ulceration with two out of four other features: recurrent genital ulceration, eye lesions, skin lesions, and positive pathergy test, are required to make the diagnosis of BD.³ In our patient, the initial differential diagnosis included a cerebral vascular event or postconcussive syndrome, with subsequent cognitive and behavioral changes. However, recurring physical symptoms suggestive of a systemic illness led to reconsideration of the diagnosis, and further work-up indicated a chronic inflammatory condition. He fulfilled ISG criteria based on recurrent oral and genital ulcers, and skin lesions. He also had monoarticular arthritis. Although cranial MRI findings were consistent with those in CNS involvement in BD,¹¹ he did not have prominent neurological signs or symptoms. Although HSV−1 was considered in the differential diagnosis, the nature of his oral/genital lesions and other clinical evidence supported the diagnosis of BD (HSV−1 is also the most common infectious agent associated with BD).¹²

There have been only a few case reports of patients presenting initially with psychiatric symptoms who were subsequently diagnosed with BD, mostly from regions where BD is more prevalent.^13,14 Very few U.S. cases of BD with prominent psychiatric problems have been described.^15,16 In our patient, the abrupt onset of neuropsychiatric symptoms in a previously healthy person without a significant family history of psychiatric disorders, atypical presentation for his age, and persistent symptoms suggest that his behavioral and cognitive symptoms were due to CNS involvement in BD. However, it is difficult to determine how and to what extent our patient’s neuropsychiatric symptoms are related to the brain lesions seen on MRI. Steroids and/or immunosuppressive therapy are used to treat BD with CNS involvement,⁷ and improvements after treatment have been noted in psychiatric and neurological symptoms as well as radiological findings.^13,17

This case report of BD in an African American man with initial psychiatric presentation illustrates potential pitfalls of misdiagnosis or delayed diagnosis when the underlying disease is rare. Furthermore, the presence of behavioral and cognitive symptoms can further contribute to the delay in diagnosis, as was the case with our patient, who was not forthcoming about his symptoms, particularly the genital lesions, and was irritable when approached. This case also underscores the importance of considering unusual presentations of seemingly rare conditions in the differential diagnosis, even though they are considered rare in certain demographic and geographic distributions. Patients with symptoms suggestive of BD would most likely present to a dermatologist or rheumatologist. However, our case highlights the need for heightened awareness among psychiatrists and neurologists to consider systemic illness as a possible underlying etiology when encountered with an atypical neuropsychiatric presentation suggesting an organic etiology. Furthermore, the value of a careful and thorough physical exam also cannot be overemphasized.

Conclusions

Diagnosis of BD remains clinical. It can affect multiple systems, and involvement of the CNS can be a negative prognostic factor. It is important for psychiatrists and neurologists to consider BD in the differential diagnosis of atypical neuropsychiatric presentation, especially when these are accompanied by recurring oral, genital, and dermatological lesions, and characteristic radiological findings. Timely recognition and correct diagnosis can have significant treatment and prognostic implications.