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Clinical experience of BD and COVID-19

This page aims to collect clinical experience of BD and COVID-19. Previous experience is always worth taking into account and may be helpful pending publication of robust scientific evidence in due course.

Please send clinical experience, however brief, to Dorian Haskard at [email protected]. Submissions will be reviewed within ISBD prior to inclusion on this page.

22nd January 2021 Reports of three cases of COVID-19 in Behçet’s disease patients in Tunisia

Case 1 from Professors Maya Abdallah MD and Mohamed Habib Houman MD, Internal Medicine, Faculty of Medicine, University Of El Manar Tunis, Tunisia.

The patient is a 28-years old man. He had been diagnosed with Behçet’s disease since November 2019 with oro-genital ulcers, and cutaneous lesions (erythema nodosum (EN), pseudofolliculitis. He was treated with colchicine 1mg/d. In September 14th, he called his physician for fatigue, headache, fever, and myalgia. He was tested positive for SARS-CoV-2 infection by RT-PCR performed on nasopharyngeal swabs (NPS). He did not stop taking Colchicine. He did not come back to see his doctor but he self-medicated by amoxicilline 3g/d and paracetamol 3g/d. The symptoms resolved quickly in 5 days. He saw his physician after a week in good health. Until now, he’s asymptomatic.

Case 2 from Professors Maya Abdallah and Mohamed Habib Houman, Internal Medicine, Faculty of Medicine, University Of El Manar Tunis, Tunisia

The patient is a 47-year-old woman. Since October 2019 she was diagnosed with Behçet’s disease with recurrent oral and genital ulcers for several years, pseudofolliculitis and oligoarthritis. Her treatment consisted of colchicine 1mg/d only. At the beginning of January 2020, she stopped taking colchicine. On the 1st of October 2020, she called her physician for fatigue, myalgia, headaches, and dysgeusia. She was tested positive for COVID-19 by a SARS-CoV-2 by RT-PCR performed on nasopharyngeal swabs. She did not contact her physician, but she auto-medicated with vitamin C and paracetamol. She improved, and in days all her symptoms but dysgeusia disappeared. This last symptom persisted till December 2020 when she saw her physician who prescribed the resumption of colchicine. Dysgeusia improved slowly and disappeared completely in 15 days.

Case 3 from Professor Mohamed Habib Houman, Internal Medicine, Faculty of Medicine, University Of El Manar Tunis, Tunisia

A 66 years old woman, with a past history of hypothyroidism post thyroidectomy for benign nodules treated by levothyroxine (2010); asthmatic chronic bronchitis treated with miflonid breezhaler and inhalation corticosteroids (if needed) (2017); colonic angio-dysplasia (2018). In 2015 she was diagnosed with Behçet’s disease:

oral and genital ulcers for several years
erythema nodosum (2013)
pseudofolliculitis
oligoarthritis
inferior left leg superficial thrombophlebitis
splenic arterial aneurysm treated with corticosteroids and azathioprine besides colchicine. It significantly diminished in diameter over months.
neurological involvement when taking daily prednisone 10 mg, azathioprine 100 mg, colchicine 1mg and levothyroxine 75µg. it consisted of headaches, pyramidal syndrome and sensory ataxia. Angio MRI showed subcortical and periventricular white matter hyperintensities lesions on T2/flair signals. No vascular lesion was seen. Treatment consisted of 1 daily pulse of methylprednisolone during 3 days followed by oral prednisone tapering progressively to 5mg/d as well as 6 monthly pulses of cyclophosphamide followed by azathioprine 150 mg/d. The neurological manifestations disappeared in about 8 months

The patient remains stable until December 2021 when she was diagnosed with COVID-19. On December 15^th, she developed headaches, fever, myalgia, dry cough, shortness breath, burning sensation in the upper airways including the nose, and tachycardia. She was tested positive for SARS-CoV-2 by RT-PCR performed on nasopharyngeal swabs. She was isolated at home where he was treated with:

Azithromycin
A single dose of 2000 000 UI of Vitamin D
Vitamin C 1g a day during 1 week
Zinc 1 pill/d during 15 days
Enoxaparin 4000 UI 1 injection/d for 2 weeks

And continued to take colchicine 1mg, azathioprine 100 mg and levothyroxine 75.

Then, 1 day later after her familial physician added 60 mg/day of prednisone.

She did not improve and in the 4^th day she developed stomach ache, nausea, vomiting, and remained polypneic and tachycardic. She was admitted to the Department of Internal Medicine. CBC showed leucopenia at 2300/ml, D-dimers were at 230 ng/ml. The oxygen saturation level (SaO2) was at 93 %. Chest CT scan did not show any significant abnormalities. We did not observe signs evoking SARS-CoV-2 infection nor pulmonary embolism.

Oxygen supply by nasal cannula (2 liters) was delivered. We stopped prednisone one and prescribed oral dexamethasone 6 mg once daily for 10 days. Azathioprine and colchicine were stopped due to leucopenia. She was in hospital for 7 days with significant improvement; the SaO2 was at 97-99%.

Her husband was also infected.

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New publication: Yurttas, B., M. Oztas, A. Tunc, Balkan, II, O. F. Tabak, V. Hamuryudan, and E. Seyahi. "Characteristics and Outcomes of Behcet's Syndrome Patients with Coronavirus Disease 2019: A Case Series of 10 Patients." Intern Emerg Med 15, no. 8 (2020): 1567-71. https://www.ncbi.nlm.nih.gov/pubmed/32647946

8th December 2020 - Professor Jan van Laar and S. den Otter report nine more COVID-19 BD patients in the Netherlands:

The first patient is a 32 year old female. She was admitted with COVID-19 pneumonia. She had been diagnosed with Behçet’s disease since 2012 with oro-genital ulcers, cutaneous lesions, a positive pathergy test and gastro-intestinal symptoms. Her treatment includes Humira which was started in 2017. In October she developed fever and shortness of breath. Soon hereafter she tested positive for COVID-19. Humira was stopped and the symptoms subdued after 2 weeks and she restarted Humira.
The second patient is 57 year old female who had been diagnosed with Behçet’s disease since 1997. Since 2012 the disease activity is very low and was treated with colchicine on demand. The patient has a BMI of 35.86 kg/m². In the first week of October she developed retrosternal pain mid-left and tested positive for COVID-19. A few days after she developed progressive shortness of breath and was admitted to the hospital where she was treated with remdesevir, dexamethasone and a high dose prophylaxis of LMWH. During hospitalization she needed non-invasive ventilator support and was complicated by development of steroid induced diabetes and remdesevir-induced reversible hepatic enzyme elevations. After a total of 15 hospitalized days she was discharged. During the hospitalized days she did not use the colchicine, and concurrently there were no symptoms of active Behçet’s disease.
The third patient is a 47 year old HLA-B51 positive male. Since 2007 he is diagnosed with Behçet’s disease with oral and genital ulcers, pustules and oligoarthritis. His treatment includes Humira, colchicine and NSAID’s. Mid-septemeber he developed shortness of breath and tested positive for COVID-19. The Humira was stopped. The respiratory symptoms resolved quickly and Humira was restarted.
The fourth patient involves a 28 year old male who had been diagnosed with Behçet’s disease with mucocutaneous and vascular activity since 2015. Since august 2020 he started apremilast. After a week he developed high fever, anosmia and shortness of breath. He tested positive for COVID-19. After two weeks his symptoms disappeared and a month after the disappearance of the symptoms he resumed apremilast.
The fifth patient is a 20 year old male. Since 2012 he is diagnosed with Behçet’s disease. He had originally presented at the age of 12 with cavernus sinus thrombosis. In October 2020 he developed aortitis due to vascular Behcet’s disease. His treatment includes colchicine, infliximab and prednisone for the aortitis. At the third week of October he developed a cold and four days after anosmia. His fiancé tested positive for COVID-19 and so did he. Infliximab was temporarily discontinued.
A 34 year old female was admitted with COVID-19 pneumonia. Since 2019 she has been diagnosed with Behçet’s disease with orogenital ulcers and uveitis. Her treatment includes azathioprine. She tested positive for COVID-19 and had mild symptoms (no fever) for two days during which azathioprine was stopped.
A 46 year old male was admitted with COVID-19 pneumonia. He has been diagnosed with Behçet’s disease with orogenital ulcers and cutaneous manifestations. His treatment includes colchicine. Begin of November he developed coughing, a sore throat, shortness of breath, muscle aches and anosmia. After this he tested positive for COVID-19. During the infection his treatment was not discontinued.
The ninth patient includes a 46 year old HLA-B51 positive female who had been diagnosed with Behçet’s disease with orogenital ulcers since 2019. S colchicine and recently had COVID-19 with mild symptoms. Her treatment was not discontinued and she improved swiftly.

10th Sept 2020 - Professor Jan van Laar reports from Rotterdam (Netherlands): Two new cases of Behçet’s patients with COVID-19 infections are reported from the Netherlands.

The first patient involves a 34 year old woman of Moroccan descent. She had been diagnosed with Behçet’s disease since 2019 with panuveitis, oro-genital ulcers and pustular skin lesions. Her treatment includes azathioprine and steroid applications. In the first half of August she was tested positive for COVID-19 after her husband was infected. Five days later she developed afebrile influenza-like symptoms and anosmia. Azathioprine was stopped and the symptoms subdued after two weeks and she restarted azathioprine.

The second patient is a 28 year old HLA-B51 positive Syrian male with oro-genital ulcers, cutaneous manifestations and recurrent deep venous thromboses. He also has mild osteogenesis imperfecta with a heterozygous COL1A1 mutation. His treatment includes colchicine and Apremilast which was started in August 2020. Soon hereafter he developed influenza-like symptoms and was tested positively for COVID-19. Within 2 weeks all symptoms subdued and he restarted Apremilast.

22th Jun 2020 - Dr Fatma Alibaz-Oner and colleagues report from Marmara University School of Medicine (Turkey): We have had one 1 BD patient with COVID-19. This was a 36 years old male patient who applied to our Behçet’s Clinic due to contact with a confirmed COVID-19 positive patient. Behçet’s disease was diagnosed at the age of 23 when he presented with oro-genital ulcers, erythema nodosum-like cutaneous lesions and pathergy positivity. We have been treating him with infliximab (INF) together with azathioprine for 2 years due to refractory vascular involvement (deep venous thrombosis and pulmonary thrombosis). He achieved complete remission after infliximab treatment. He had no other comorbidity and no smoking history. He had no symptoms from COVID-19 infection, but had positive COVID-19 PCR test. When PCR was detected positive, he was in the period between two routine INF infusions. He took 5 days of hydroxychloroquine treatment, and continued to take daily azathioprine. During the follow-up quarantine period, he did not have any symptoms. His thorax CT was normal. His second PCR test was negative just before the routine INF infusion. Therefore his INF infusion was given in the scheduled date.

19^th June 2020 – Professor Jenaro Graña Gil and colleagues report from Coruña (Spain): Only 2 of 55 BD patients under active follow-up have developed COVID, one of whom is included in a series of COVID in inflammatory rheumatic disease from around Spain (https://doi.org/10.1101/2020.05.11.20097808)

Case 1 was a 73-year-old male patient, who in 1987 (40 years old) underwent surgery for a right femoral aneurysm that was associated with Behçet syndrome due to the presence of oral aphthosis, occasional genital lesions, episodes of inflammatory colitis and previous episodes of folliculitis and superficial phlebitis. He received cyclophosphamide treatment for 6 months and then azathioprine. He had several episodes of uveitis 10 years after the aneurysm episode. He had cyclosporine treatment for 5 years. Since then, he was asymptomatic for BS and without immunosuppressive treatment but has developed osteoarthritis of the knees, ischemic heart disease with the need for coronary stents and valvuloplasty due to severe mitral regurgitation in May 2019, and primary hyperparathyroidism. in the last 10 years, he has not received any specific treatment for Behçet syndrome. He has had 2 visits per year in the monographic BS consultation and has had knee infiltrations due to osteoarthritis but has not presented any reactivation of BS. Cardiovascular disease could not be associated with an inflammatory cause and is considered arteriosclerotic. In March 2020, PCR was determined for possible family infection by SARSCOV2, which was positive on 2 occasions, although he remained oligosymptomatic at home and evolved favourably.
Case 2 is a 63-year-old woman. Since the age of 35 she has frequent episodes of oral aphthous lesions. At age 40, she began with self-limited episodes of anterior uveitis with a good response to topical treatment. Since then, she also has one or two episodes a year of nodular skin lesions with a good response to non-steroidal anti-inflammatory drugs and short glucocorticoid cycles. She had short periods of treatment with cyclosporine but refuses to use immunosuppressants. She is taking 1 mg of colchicine daily. In April of this year, SARSCOV2 PCR was determined by family contact, which was positive. She did not have fever or respiratory symptoms but she did have a noticeable worsening of the oral lesions and she had inflammatory skin lesions on her feet and oropharyngeal inflammation that improved with a brief course of oral prednisone(30mg x 3 days, 15mg x 3 days and 10mg x 3 days).

18^th June 2020 – Professor Gülen Hatemi reports from Istanbul (Turkey): The Turkish Society for Rheumatology registry has a number of BD patients with COVID, and is in the process of publishing details. As there were no patients on interferon-alpha, it would be interesting to know whether interferon may have a protective role, considering its use in COVID-19 infection in China, and the beneficial results of the RCT with interferon beta-1b, when used together with Ribavirin and Lopinavir-Ritonavir compared to Lopinavir-Ritonavir alone (Hung et al. Lancet. 2020;S0140-6736(20)31042-4).

16^th June 2020 - Professor Houman Habib reports from Tunis (Tunisia): During the last 4 months, the number of patients who have consulted us has dropped drastically for fear of being infected with COVID-19. And In addition, we did not accept non-emergency patients either in the hospital or in our outpatient clinic for 1 month and a half. So, the number of patients was low compared to the non-epidemic period. In fact, I have not seen any BD patient with COVID-19, and I can confirm that this is also the case in Tunisia as a whole.

12^th June 2020 - Professor Jan van Laar reports from Rotterdam (Netherlands): A 54 year old male was admitted for 3 weeks with severe respiratory symptoms. Behçet’s disease was diagnosed at the age of 22 when he presented with oro-genital ulcers, cutaneous lesions and a positive pathergy test, with HLA-B51 positivity and superficial and deep venous thromboses. All this time he was effectively treated with local applicants, colchicine and later low doses of azathioprine. Earlier this year he was diagnosed with nasopharyngeal cancer and treated with chemo-radiation therapy. After the second course he developed fever, coughing and dyspnea and was hospitalized for impending respiratory failure. He was diagnosed with COVID-19 bilateral pneumonia and treated with antibiotics and oxygen supply. After three weeks he could be dismissed. Three out of his four resident family members were also infected.

20^th April 2020 - Professor Jan van Laar reports from Rotterdam (Netherlands): A 21 year old female was admitted with COVID-19 pneumonia. She had originally presented aged 8 with fever and oral aphthous ulcers. Later on she developed vaginal ulcers, pustules and neurological symptoms, and also severe condylomata and warts on the hands. She has long been treated with prednisone and Remsima six-weekly (anti-TNF alpha). She mentioned that she easily acquires upper respiratory infections, presumably viral. She did not have any known risk factors for COVID-19 complications such as cardiovascular disease or obesity. She was in hospital for 7 days and recovered fully after antibiotics and oxygen supply by nasal canula. There was no clinical evidence of thrombosis.

March 2020 - verbatim report from an Ophthalmologist in China "So far, we have not seen any evidence regarding the influence of immunosuppressive drugs on coronavirus infection. No uveitis visiting my department reported coronavirus infection and we have not heard coronavirus infected patients from other departments complain suffering from vision loss, thus no change of the treatment."