A young lad about 12 years of age was brought by his father for treatment from their home town of Bahawalpur to Karachi. The boy and his father had slightly different stories to tell and also his father had more information of the treatment received and the opinion of other doctors who had seen the young patient, the examiner’s decided to request the father to stay with the patient to answer the candidates questions, The father had been told not to say anything unless the candidate asked him a direct question.
The history was that he boy had suffered from recurrent episodes of fever for one year. We needed to know why. The young boy had multiple soft mobile swellings just under the skin, One was on the medial aspect of the elbow about 3 inches long and 11/2 inches wide, there was a similar one slightly smaller on the back of the left elbow and one on the scapula. He was emaciated, but otherwise bright. his lymph nodes were not enlarged. His spleen was 3 cm enlarged and was firm. The liver was not enlarged. N one in the close family had tuberculosis and he had not been in known contact with a TB patient in his school. What information was needed to identify the problem and proceed further?
The pattern of the fever was periodic. The father said that the boy got better after 3-4 weeks and went back to school but the fever came back sometimes for a week or ten days. He had received multiple courses of malaria and “typhoid” according to the fever, even IV antibiotics were used. The father gave a history of having bought some animals a year ago. a cow and 5 goats and kept them at home for several months until the Eid sacrifice. During this time the cow needed to be treated by the veterinarian. Only the father gave this history. Both candidates who had this patient as a long case asked if the family lived in the city. When the answer was yes they did not ask for a history of exposure to animals. One candidate chose not to speak to the father at all!!!
What questions should have been asked?
How long have these swellings been there? The boy said one year but his father clarified that these had been there since the patient was a little boy but had been smaller in size. Have any of these swellings recently become red, warm, painful to touch and “tight” i.e. grown suddenly overnight? Have new swellings been appearing? The answer was no the swellings are soft and do not hurt. In fact they were lipomata which may or may not be part of neurofibromatosis.
Details of the fever. If the fever persisted for a few days say 5-10 days then settled for 3-4 weeks and then recurred think of the Pel Epstein pattern of fever in Hodgkin’s lymphoma. The fever settled after 10-14 days, the patient was well, had lost all symptoms of disease like night sweats, body aches, had regained his appetite and full physical activity and then the fever came on again with all the previous symptoms 48 hours to 2 months later: think of a relapse which can occur in typhoid fever (but not more than 2 times; typhoid is very unlikely to last a year) and brucellosis in which 15% of people experience recurrent relapses for up to a year. If the fever has persisted for a year with night sweats, weight loss, poor appetite then think of tuberculosis, chronic brucellosis, lymphoma possibly sarcoidosis. Persistence of infection may occur in tissue less well penetrated by antibiotics such as bones, middle ear and joints. Ask questions about those: bone pain specially in a long bone occurs not only in leukemia but brucellosis or tuberculosis which can cause osteomyelitis. Ask about joint pains and backache specially lower back pain. Involvement of the spine and sacroiliac joint can occur in brucellosis, tuberculosis. When is low back pain dangerous? When it is accompanied by any of the following; fever, night sweats, weight loss, poor appetite, history of trauma or malignant disease i.e. having received chemotherapy or radiation, or if there are accompanying neurological signs such as spinal cord compression or nerve compression resembling sciatica or if there is loss of sensations. Significant arthralgia can occur in brucellosis, tuberculosis. sarcoidosis, SLE (remember 1 out of every ten cases of SLE is a male).
Here brief systemic survey may come in handy. Ask about earache or ear discharge, nodules in the neck and axilla other than the lipomata, any cough, chest pain or breathlessness, or abdominal pain or cramps or diarrhoea though it is unlikely that these symptoms will have been forgotten and not mentioned by the patient. Ask about a rash and joint pain and a bleeding tendency. Ask whether the boy had handled the animals specially the sick cow. Ask if he drinks unboiled fresh milk (some people think unboiled milk has more food value and vitamins but it also has the bacteria causing tuberculosis, brucellosis and typhoid fever), rather than pasteurised milk from a tetrapack. Do your legs feel stiff or weak? Dou tend to stumble or fall? These are significant questions and you should be able to tell the examiner why you are asking them.
I have discussed the diagnosis of tuberculosis in one of my blogs. Let us discus briefly about brucellosis which all of you forget to read. Brucellosis is a zoonosis. The organisms Brucella abortans (cows), Br millitensis (goats) occur in cows and goats and Br suis in pigs and Br canis dogs are infective to man, sheep and small rodents have brucellosis but the disease is probably not transmitted to humans. The organism is present in the blood, urine, milk, placenta and aborted material of the infected animals. People who slaughter the animals, care for them, sell meat, prepare food are likely to be infected. Veterinarians and laboratory workers are susceptible. The organisms are very small intracellular Gram-negative rods with no fimbria or cilia or spores. Bacterial growth is slow. The classic biphasic (solid and liquid) blood culture technique of Ruiz-Castaneda is still used in developing settings, but automated blood culture systems like Bac-tec are more effective . Colonies are usually 0.5 to 1.0 mm in diameter, raised and convex, with an entire edge and a smooth, shiny surface.
Brucella organisms can survive up to two days in milk at 8°C (they will survive in the non-freezer compartment of a refrigerator), up to three weeks in frozen meat, and up to three months in goat cheese. Brucellae shed in animal excretions may remain viable for >40 days if the soil is damp. The organisms are sensitive to heat, ionizing radiation, most commonly used disinfectants, and pasteurization.
Acute brucellosis usually consists of the insidious onset of fever, night sweats (with a strong, peculiar, moldy odor), arthralgia, myalgia, low back pain, and weight loss as well as weakness, fatigue, malaise, headache, dizziness, depression, and anorexia. A significant percentage of patients may have dyspepsia, abdominal pain, and cough. Physical findings are variable and nonspecific. Hepatomegaly, splenomegaly, and/or lymphadenopathy may be observed. The fever in untreated acute brucellosis can be high or slightly elevated and usually lasts for days to weeks. Irregular undulation has been described. Brucellosis can be a cause of fever of unknown origin.
Localized infection — Focal infection occurs in about 30 percent of cases:
- Osteoarticular involvement is the most common presentation. The sacroiliac joints and large joints of the lower limbs are most frequently involved. Spondylitis is a serious complication of brucellosis; it is more prevalent in older patients and patients with prolonged illness prior to treatment. The lumbar vertebrae are involved more frequently than the thoracic and cervical vertebrae.
- Paravertebral, epidural, and psoas abscess can occur in the setting of brucellar spondylitis.
- Genitourinary involvement occurs in 2 to 20 percent of cases; orchitis and/or epididymitis are the most common manifestations. Less common manifestations include prostatitis, cystitis, interstitial nephritis, glomerulonephritis, and renal, testicular, or tubo-ovarian abscess .
- Pulmonary involvement occurs in up to 7 percent of patients with brucellosis. Bronchitis, interstitial pneumonitis, lobar pneumonia, lung nodules, pleural effusion, hilar lymphadenopathy, empyema, or abscesses may be observed.
- Gastrointestinal involvement can present with clinical hepatitis (3 to 6 percent of cases) . Rarely, other manifestations include hepatic or splenic abscess, cholecystitis, pancreatitis, ileitis, colitis, and spontaneous peritonitis.
- Hematological abnormalities, including anemia, leukopenia, thrombocytopenia, pancytopenia, and/or disseminated intravascular coagulation, are relatively common.
- Neurological involvement occurs in 2 to 7 percent of cases. Manifestations include meningitis (acute or chronic), encephalitis, myelitis, radiculitis, and/or neuritis (with involvement of cranial or peripheral nerves).
- Cardiac involvement is relatively rare but may include endocarditis, myocarditis, pericarditis, endarteritis, thrombophlebitis, and/or mycotic aneurysm of the aorta or ventricles. Of these, endocarditis occurs most frequently (1 to 2 percent of cases) and is the main cause of death attributable to brucellosis.
- Ocular involvement most commonly presents with uveitis. Other manifestations include keratoconjunctivitis, corneal ulcers, iridocyclitis, nummular keratitis, choroiditis, optic neuritis, papilledema, and endophthalmitis.
- Dermatologic manifestations occur in up to 10 percent of patients. Findings may include macular, maculopapular, scarlatiniform, papulonodular, and erythema nodosum-like eruptions, ulcerations, petechiae, purpura, granulomatous vasculitis, and abscesses.
Relapse — The rate of relapse following treatment is about 5 to 15 percent . Relapse usually occurs within the first six months following completion of treatment, although it may occur up to 12 months following completion of treatment. Most common cause is delayed treatment, stopping the treatment too early and use of wrong antibiotics.
Chronic brucellosis refers to patients with clinical manifestations for more than one year after the diagnosis of brucellosis is established. Chronic brucellosis is characterized by localized infection (generally spondylitis, osteomyelitis, tissue abscesses, or uveitis) and/or relapse in patients with objective evidence of infection (elevated antibody titers and/or recovery of brucellae from blood or tissues). In some cases, patients attribute symptoms to chronic brucellosis in the absence of objective evidence for infection (low antibody titers, sterile cultures). Such patients typically have a cyclic course with intermittent back pain, arthralgia, sweats, and signs of psychoneurosis.
Confirming the diagnosis.
- Bone marrow culture using lysis centrifuge technique is the gold standard, blood and other body fluids may be cultured. Since the growth is biphasic the Ruiz-Castenada technique is used.
- Liver, lymph node and other biopsy materials show non-caseating granulomas with no epitheloid cells. In this brucellosis resembles sarcoidosis.
- Serological methods include:
- Serum agglutination (standard tube agglutination)
- Enzyme-linked immunosorbent assay
- Rose Bengal agglutination
- Coombs test
- Immunocapture agglutination (Brucellacapt)
- 2-mercaptoethanol agglutination
- PCR can be performed on blood or other body fluids.
- Imaging — Patients with spine symptoms should have an MRI examination to rule out spinal cord compromise. Localized snowflake calcification in chronic hepatosplenic brucellosis is the only specific radiographic finding that may be used to distinguish brucellosis from other diseases.
- Treatment. In adults 2 regimes are used.
- Oral doxycycline 100 mg twice a day for 6 weeks along with streptomycin injection 1 gm IM daily for 14-21 days.
- Oral doxycycline 100 mg twice a day along with rifampicin 15mg/kg (600-900 mg) once daily for 6 weeks.
- In children trimethoprim/sulphamethoxazole along with rifampicin may be used for 6 weeks. Add streptomycin if there is osteomyelitis.
- In pregnant women the choice of treatment is difficult but TMP/SMX along with rifampicin or streptomycin (gentamicin) can be used. TMP/SMX should be avoided in the last trimester as there is a risk of kernicterus. Rifampicin with ceftriaxone may be used instead.
- Other drugs. Ciprofloxacin or ofloxacin may be used along with rifampicin.
- Treatment of a relapse. Look for a local focus like an abscess. Repeat a standard course of therapy.