Complications of measles: a case series

Abstract

Measles, which was once thought to be a disappearing viral infection due to effective vaccination, has been re-emerging globally, with increasing cases in adolescents and adults. This has been attributed to anti-vaccination campaigning in the early 21st century, which has resulted in a drop in overall herd immunity. In this case series we report three patients with complications secondary to measles who presented to a hospital in Malta in 2019. Through this series, we discuss the range of possible complications caused by the measles virus, ranging from mild viraemic symptoms to multiorgan involvement which could possibly lead to high-dependency care and may even be fatal. We also highlight recent global statistics which reflect the exponential increase in the incidence of measles, with a special focus on Europe. It is emphasised that vaccine education and compliance with the two-dose measles vaccine should be implemented worldwide.

Background

Measles, a paramyxovirus, is a highly contagious viral respiratory illness characterised by a prodrome of fever along with cough, coryzal symptoms and conjunctivitis.¹ This is followed by a pathognomonic maculopapular rash, starting from the head down to the trunk and lower limbs including the palms and soles. It may also present with Koplik's spots as an enanthema.

Complications from the measles virus have been reported in every organ system. We present three cases with three similar presentations but different complications. With the current global outbreak of measles, we emphasise the importance of an immunisation history in the medical clerking and serology as the diagnostic modality whenever there is a low clinical suspicion for measles.² Urgent efforts are needed to ensure global coverage with two-dose measles vaccines through education and strengthening of national immunisation systems.

Case presentations

Case 1

A 29-year-old Maltese man without a significant past medical history presented with a 4-day history of intermittent fever associated with chills and rigours, nausea and multiple episodes of vomiting. A generalised maculopapular pruritic rash developed on the second day and he was sent to hospital for further investigation. On general examination the patient was haemodynamically stable with a temperature of 38°C. An exanthematous maculopapular rash was evident over the face, trunk and lower limbs including the soles of the feet (figure 1). No Koplik spots were found. On examination there was tenderness in the right upper quadrant of his abdomen.

Figure 1.

Case 1. Macular confluent rash over the soles of the feet.

Investigations

Initial blood investigations showed a lymphocytopenia of 0.35×10⁹/L (range 1.3–3.6×10⁹/L) and liver derangement with a hepatitic picture (GGT 257 U/L with 65 U/L upper limit of normal and ALT 650 U/L with 11 U/L upper limit of normal). Urine and blood cultures were negative and chest x-ray was normal. Abdominal ultrasound imaging was within normal limits. IgM and IgG antibodies using Enzyme Linked Immunosorbent Assay (ELISA) for measles were found to be positive.

A diagnosis of measles complicated with hepatitis was made.

Differential diagnoses

The differential diagnoses included hepatitis, infectious mononucleosis, HIV, cytomegalovirus, syphilis and rubella. All were excluded through negative rapid serological assays.

Treatment, outcome and follow-up

Supportive care was given with intravenous fluids. After 3 weeks the patient recovered without any further sequelae and liver function improved. It was noted that the patient had only taken one dose of the two-dose MMR vaccine in childhood.

Case 2

An 18-year-old British woman, on holiday in Malta, presented with a 3-day history of a pruritic generalised macular erythematous rash over her trunk (figure 2), face and limbs. She also complained of a prominent dry cough with oxygen desaturation of 89% on room air despite a clear chest, myalgias and right iliac fossa tenderness on palpation, exacerbated by movement. Faint Koplik's spots were evident on examination. The patient had never received the MMR vaccine.

Figure 2.

Case 2. Pathognomonic confluent macular rash over the trunk.

Investigations

A diagnosis of measles was confirmed with positive IgG and IgM antibodies using ELISA. Koplik's spots swabs sent for measles IgM, IgG and PCR were also positive. A plain chest x-ray was normal but a CT of the trunk showed an enhanced fluid-filled appendix confirming appendicitis (figure 3).

Figure 3.

Case 2. CT scan of the abdomen showing appendiceal wall inflammation and oedema secondary to appendicitis (marked with a yellow arrow).

A diagnosis of measles appendicitis was made.

Differential diagnoses

Other viral infections with a similar clinical picture such as hepatitis, HIV, syphilis, rubella and infectious mononucleosis were again excluded.

Treatment, outcome and follow-up

The patient improved with supportive care and broad-spectrum antibiotics and recovered within 2 weeks. Surgical intervention was not required. CT of the thorax excluded possible measles pneumonitis or pneumonia. Respiratory symptoms were attributed to a co-existing viral respiratory tract infection which improved with supportive care.

Case 3

A 42-year-old man who had been diagnosed with measles by his general practitioner following positive IgM antibody using ELISA for measles presented 1 week later with bilateral blurring of vision. This was associated with eye irritation and a conjunctival discharge. He also complained of compressive, moderate to severe occipital headaches radiating to the front. These were associated with mild phono- and photophobia; there was no associated nausea, vomiting, hallucinations, confusion or aggression.

On examination the patient was afebrile with mild neck stiffness. An ophthalmic review confirmed no papilloedema but he was found to have bilateral pseudodendritic lesions which were treated with dexamethasone eye suspension for 7 days.

Investigations

A CT of the brain confirmed no structural pathology. A lumbar puncture confirmed viral meningitis and he was diagnosed with meningeal involvement secondary to measles infection.

Differential diagnoses

A similar clinical picture could be seen in other viral infections such as cytomegalovirus infection, which were excluded with PCR testing. A baseline viral screen including hepatitis and HIV were also taken with patient consent.

Treatment, outcome and follow-up

The patient improved significantly with supportive care over the next 2 weeks, without any neurological sequelae.

Discussion

Complications from measles have been reported in every organ system as the virus targets epithelial, reticuloendothelial and white blood cells causing immunosuppression.³ Measles virus infection leads to a decline in CD4 lymphocytes, starting before the onset of the rash and lasting for up to 1 month, resulting in suppression of delayed-type hypersensitivity.⁴

According to the Centers for Disease Control and Prevention, approximately 30% of reported measles cases have one or more complications. These occur most commonly in children under 5 years of age and adults above 20 years of age. Currently, there are no reliable available data regarding the incidence of specific complications.⁵

Respiratory complications are the most common, presenting with pneumonitis, pneumonia or bacterial suprainfection. The severity depends on how critically ill the patient is, with intensive care being required in some cases.²

Neurological sequelae range from benign febrile seizures, mostly in children, to viral meningitis, to postinfectious encephalomyelitis (PIE). PIE is more common in adults and presents with sudden onset of new fever, altered mental status, seizures and multifocal neurological signs. Studies have shown that the virus is usually not identified in the central nervous system and symptomatology is secondary to an abnormal immune response that affects myelin basic protein.⁶ Unlike PIE, measles antibody is present in cerebrospinal fluid in subacute sclerosing panencephalitis (SSPE), another complication of measles.⁷ Both conditions cause neurological deficits, but SSPE causes permanent damage leading to vegetative state.

A nationwide study of severe measles infection in critically ill adult patients requiring intensive care in France showed that measles-associated pneumonitis and, less commonly, post-infectious encephalomyelitis are the the most common complications, worsening morbidity and mortality.⁸ Young adults, pregnant women and immunocompromised patients are at a potentially higher risk of such complications.

Gastrointestinal complications include measles-associated diarrhoea with secondary dehydration and cases of appendicitis have also been reported. Characteristic giant cells positive for measles can be seen on immunologic staining of gastric or appendiceal biopsies, which may be present before the emergence of the pathognomonic rash.⁹

Conjunctivitis is common in measles and can lead to keratitis, detectable by slit-lamp. In well-nourished immunocompetent patients, these lesions usually heal without any residual damage.¹⁰ However, suprainfection may lead to permanent scarring and blindness. A Cochrane review by Bello et al ¹¹ showed that vitamin A deficiency predisposes to more severe ocular complications and is one of the most common causes of acquired blindness in children in developing countries.

Measles is a vaccine-preventable disease. Despite the availability of a safe and cost-effective vaccine, in 2017 about 110 000 measles deaths were reported globally according to the World Health Organization (WHO), mostly among young children. Large outbreaks with fatalities are currently ongoing in European countries which had previously eliminated or interrupted endemic transmission.

According to the European Centre for Disease Prevention and Control,¹² there have been more than 10 000 cases of measles reported in Europe since the beginning of 2019 up to mid-July, with the highest numbers being in France, Bulgaria, Italy, Poland and Lithuania. This is also reflective of the Maltese Islands which, for a population of half a million, have seen a burst of notified cases of measles with the local Infectious Disease Prevention and Control Unit reporting 29 cases of measles this year to date compared with only one case in 2018 and no cases in the previous 3 years. Almost all cases seen this year have occurred in adults aged 23–45 years.

These outbreaks are attributed to declining vaccination levels, mostly due to publicity in the early 2000s related to the conflicting hypothesis that the MMR vaccine can cause autism, despite significant national studies proving otherwise.¹³ This has had a global impact with a decrease in herd immunity to measles resulting in its increasing emergence. Thus, global strategies are required to optimise vaccine coverage with a surveillance programme in accordance with WHO recommendations.

Learning points.

• Measles is a viral illness which can be prevented with appropriate immunisation.

• The diagnosis of measles should be suspected in anyone presenting with fever and a maculopapular rash.

• Measles infection may be associated with complications affecting different organs.

• Global frameworks promoting and implementing two-dose measles vaccination to all ensures an increase in herd immunity worldwide.