A private hospital’s approach to treating acute familial Mediterranean fever in Dar es Salaam

Introduction

Familial Mediterranean fever (FMF) is a hereditary autosomal recessive autoinflammatory disorder characterized by recurrent bouts of fever and serosal inflammation, which includes peritonitis, pleuritis, pericarditis, synovitis, and erysipelas-like erythema.^1,2 The initial attack occurs before the ages of 10 and 20–30 years in 65% and 90% of cases, respectively. FMF can affect individuals of any ethnic group, but the rates are much higher for certain Mediterranean populations, including individuals of Armenian, Turkish, Middle Eastern and North African Jewish, and Arab descent. ³ Turkey is probably said to be the country with the highest prevalence of FMF, with estimated patients of 100,000 (1:400–1:1000), followed by Israel with estimated patients of 10,000 (1:1000). Other countries include North African countries, Greece, Italy, France, Germany, and the United States.^2,4 However, extremely limited data on its occurrence is reported in East Africa, to the best of our knowledge.

The risk factors triggering the attacks include vigorous exercise, emotional stress, concurrent infections, exposure to cold, surgery, and menstruation.^5,6 FMF commonly presents with recurrent fever, abdominal pain with signs of peritonitis, chest pain due to pleural inflammation, and monoarticular joint pain involving one of the large joints. Additionally, tender, raised, and erythematous-erysipelas-like skin lesions are also observed. ⁴ Other manifestations include myalgia, acute scrotum, headache, and aseptic meningitis. ⁵

Elevation of serum markers of systemic inflammation, including leukocytosis with a predominance of neutrophils, as well as elevated acute phase reactants such as erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), serum amyloid A protein, and fibrinogen, is normally seen in acute attacks of FMF.^2,4,6

The diagnosis of FMF is based on clinical symptoms, supported by ethnicity and family history. Genetic testing is used to further confirm the diagnosis of FMF. Various diagnostic criteria, such as the Tel Hashomer criteria, Livneh’s criteria, and for the pediatric population, Turkish FMF pediatric criteria, can be employed to aid in the diagnosis of FMF.^6–8

In this context, we present a case report of a 34-year-old Egyptian gentleman who presented at the emergency department with a history of lower abdominal pain and other clinical manifestations suggestive of FMF. We describe the diagnostic process based on clinical symptoms and proceed with the management approach utilizing colchicine prophylaxis. This case report sheds light on the importance of early diagnosis and proper management of FMF, particularly in regions with limited genetic testing availability. Moreover, it emphasizes the need for further research in sub-Saharan African countries to enhance our understanding of FMF and improve patient outcomes.

Case report

A 34-year-old Egyptian gentleman presented at the emergency department with a complaint of lower abdominal pain that had been persistent for the past 2 weeks. The pain was gradually worsening over time and was not relieved by analgesics. He also reported experiencing nausea and chest discomfort, which he claimed was somewhat relieved by self-induced vomiting.

Additionally, the patient complained of subjective fevers that had been occurring for several days before the onset of the abdominal pain. Along with the fevers, he experienced joint pain and unilateral left-sided chest pain that worsened upon inspiration. The patient also had a new-onset skin rash localized in the right abdominal region. He denied having any cough, headache, scrotal pain, or muscular pain. The symptoms seemed to be triggered by stressful work conditions and exposure to cold weather.

The patient had immigrated to Tanzania 9 months ago and worked as an electrical engineer. He had a history of cigarette smoking, with a 15 pack-year index. He was a nonalcoholic and had no known history of food or drug allergies. There were no previous records of hospital admissions or surgeries. There were no previous records of FMF attacks in the patient’s medical history. However, the patient did have a positive family history of FMF in his father and son.

The delayed clinical presentation can be attributed to a lack of knowledge regarding FMF and an attempt to attribute his symptoms to other causes, such as exhaustion and cold exposure. As FMF is relatively rare and might not be widely recognized outside of Mediterranean populations, the patient may not have been aware of the possibility of this hereditary condition. Additionally, his symptoms might have been initially dismissed as common ailments related to his work stress or exposure to cold weather. These factors might have led him to delay seeking medical attention and hindered early diagnosis and appropriate management.

On physical assessment, the primary survey did not reveal any remarkable findings. In the secondary survey, the patient was found to be alert and febrile, with no signs of pallor. He appeared moderately dehydrated and had no joint swelling. An erythematous rash was observed over the right hypochondrial region and back, as well as on both lower limbs with excoriation marks. No edema was noted. The abdomen was slightly obese and tender to touch, especially in the right and left lower quadrants. There was no muscle guarding or organomegaly, but the patient had positive rebound tenderness. Bowel sounds were normal, and the chest examination showed clear bilateral air entry. The rest of the systemic examinations were unremarkable.

To investigate the patient’s condition further, an intravenous line was established, and blood samples were collected for various tests, including full blood picture, CRP, ESR, malaria screening, serum electrolytes, renal function tests, and urine routine analysis.

The laboratory results showed a white blood cell count of 11.8 × 109/l, with a neutrophil count of 9.79 × 109/l. The hemoglobin level was 13 g/dl and the platelet count was 289 × 109/l. Malaria screening showed no parasites. The ESR was measured at 22 mm/h and the CRP level was 38.64 mg/l. The creatinine level was 68.19 umol/l and proteinuria was observed.

Upon arrival at the emergency department, the patient received immediate medical attention. He was administered intravenous paracetamol 1 g for pain relief, intravenous ondansetron 8 mg for nausea, intravenous esomeprazole 40 mg for gastric protection, and intravenous normal saline 1 l over 1 h for hydration. After this initial treatment, the patient’s pain significantly improved, and a reassessment was conducted by the medical team, leading to his admission to the internal medicine ward.

Based on the Tel Hashomer criteria, the patient met one major criterion and two minor criteria, including recurrent febrile episodes accompanied by peritonitis, synovitis, and pleurisy (major criterion), erysipelas-like erythema (minor criterion), and having a first-degree relative diagnosed with FMF (minor criterion). ⁷ According to Livneh’s criteria, the patient fulfilled all the criteria, confirming the diagnosis of an acute flare of FMF. ⁶

Upon admission to the medical ward, the patient’s oral intake was withheld until the resolution of nausea. He was maintained on intravenous ringer’s lactate fluids alternating with dextrose saline fluids at 83 ml/h. Additionally, he received intravenous paracetamol 1 g every 8 h alternating with intramuscular diclofenac 75 mg for pain management, intravenous esomeprazole 40 mg daily for gastric protection, and colchicine tablets 0.5 mg daily every 12 h for FMF management. These medications led to a significant improvement in his condition.

After 52 h since admission, the patient showed remarkable clinical improvement, with stable vital signs and resolution of nausea and vomiting episodes. His abdominal pain was well-controlled. As a result, he was discharged with a treatment plan to manage FMF effectively. The discharge medications included esomeprazole tablets 20 mg daily, paracetamol tablets 1 g every 8 h for 7 days, and colchicine tablets 0.5 mg every 12 h daily for 2 weeks to prevent future FMF attacks. The patient was educated about the danger signs to watch for and advised to see a rheumatologist for follow-up after a week.

During the follow-up visit, it was observed that all inflammatory markers had returned to normal levels, indicating a positive response to the colchicine prophylaxis. The patient reported being pain-free and was satisfied with the treatment outcomes. After discussing the benefits of continuing with colchicine prophylaxis to prevent future flares and minimize the risk of complications, the patient agreed to maintain the medication regimen. Regular follow-up visits were scheduled to monitor the patient’s progress and ensure ongoing management of FMF.

Discussion

In our best knowledge, this case is believed to be the first diagnosed and treated case of an acute flare of FMF in Tanzania. As a sub-Saharan African country, genetic testing for FMF is not readily available due to its rare occurrence in African populations. Therefore, the diagnosis and treatment of FMF in Tanzania mainly rely on clinical features.

Diagnosis of FMF is based on clinical symptoms, supported by ethnicity and family history. Genetic testing is utilized to further confirm the diagnosis in patients who meet the clinical criteria for FMF, provide counseling to at-risk relatives, and guide the therapeutic approach. ⁸ However, a definitive diagnosis of FMF can only be made on a genetic basis, as certain autoinflammatory diseases may present similarly to FMF, making genetic testing crucial for differentiation.^1,4,9

Typical FMF attacks are defined by the presence of specific features, including pain due to serositis, recurrent attacks of the same type (at least three episodes), fever (rectal temperature of 38°C or higher), and a short duration (lasting between 12 h to 3 days).^6,7 Attacks of fever alone are considered typical if they recur and have a short duration without any other detectable cause. ¹⁰ In this case, the patient had monthly attacks of fever associated with body rashes, joint pain, and joint swelling, meeting the typical attack criteria.

Patients with an acute attack of FMF usually present with episodes of fever, serositis (inflammation of serous membranes), recurrent peritonitis (inflammation of the peritoneum), arthritis (joint inflammation), pleuritis (inflammation of the pleura), or erysipelas-like skin disease. ¹¹ FMF can also lead to complications such as amyloidosis, which can result in chronic kidney disease. ¹² Studies in Germany and Italy revealed a range of symptoms observed in FMF patients, including fever, abdominal pain, articular pain, thoracic pain, skin lesions, oral aphthosis, and kidney involvement. ⁹ In this case, the patient presented with similar symptoms, such as fever, abdominal pain, articular pain, and thoracic pain, meeting the diagnostic criteria according to Livneh. ⁶

Diagnosis of FMF using Livneh’s criteria requires meeting specific combinations of major and minor criteria or supportive criteria. ⁶ In this case, the patient met the criteria for FMF diagnosis according to Livneh’s criteria (Table 1).

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Table 1.

Showing Major and Minor Criteria for Livnch. ⁶

Major criteria	Minor criteria
Typical attack of generalized peritonitis	Incomplete attack involving abdomen
Typical attack of unilateral pleuritis/pericarditis	Incomplete attack involving chest
Typical attack of mono-arthritis	Incomplete attack involving one large joint
Presence of fever alone	Exertional leg pain
	Favorable response to colchicine

(The requirements to diagnose FMF have been defined as the presence of at least one major or at least two minor criteria). ⁶

In Middle Eastern populations, where FMF is prevalent, up to 95% of patients with FMF experience episodic abdominal pain, which is consistent with the origin and presenting symptoms of our patient.^1,2 Abdominal pain and tenderness in FMF patients are due to inflammation of the peritoneum, leading to signs of peritonitis such as guarding, rebound tenderness, rigidity, and dynamic ileus. ⁶ These clinical findings can sometimes be mistaken for an acute surgical abdomen, resulting in a delay in diagnosis and even unnecessary surgeries.^7,8 In our case, the patient also presented with features of peritonism, but the point-of-care ultrasound did not reveal any abnormalities.

Recurrent abdominal attacks in FMF can lead to complications such as peritonitis, which may result in the formation of adhesions and small bowel obstruction. Colchicine prophylaxis, used to control FMF attacks, has been shown to be effective in preventing the development of peritoneal adhesions.^8,9

It is essential to differentiate FMF from other hereditary periodic fever syndromes, as they all share the common characteristic of periodic or episodic fevers. ⁹ However, each syndrome also presents with distinct clinical features that distinguish it from FMF.^9,10 Other periodic fever syndromes include periodic fever with aphthous stomatitis, pharyngitis, and adenitis (PFAPA); Tumor necrosis factor receptor-associated periodic syndrome (TRAPS); hyperimmunoglobulin D syndrome (mevalonate kinase deficiency); and cryopyrin-associated periodic syndromes. PFAPA, for instance, presents with aphthous stomatitis, pharyngitis, and adenitis, and the attacks occur every 3–4 weeks, lasting 3–7 days, unlike FMF. ¹⁰

The goals of therapy for FMF are to prevent acute attacks, minimize subclinical inflammation between attacks, and prevent the development and progression of amyloidosis. Colchicine is a widely used medication for both prophylaxis and therapeutic purposes in FMF management. ¹⁰

In conclusion, we present a case of a 34-year-old Egyptian gentleman diagnosed with FMF based on Livneh’s criteria. To manage the condition, the patient was prescribed colchicine prophylaxis, which aims to prevent acute attacks and potential complications of FMF.

Conclusion

FMF is a rare genetic disorder with low prevalence in sub-Saharan countries, but healthcare providers should maintain high clinical suspicion, especially in individuals with Mediterranean origins. Diagnosis is based on clinical evaluation and genetic testing when available, as FMF can mimic acute abdominal conditions. Management includes conservative measures for acute attacks and lifelong colchicine prophylaxis to prevent recurrent episodes and complications like amyloidosis and chronic kidney disease. However, further research is needed to understand the effects of colchicine on peritoneal adhesions. This case report highlights the first diagnosed and treated case of acute flare of FMF in Tanzania, emphasizing the need for increased awareness and research in regions with low FMF prevalence.