Three patients with puffy eyelids

What’s your diagnosis?

James H. Brien

Over the years, an old friend, Michael Cater, MD, a pediatrician at Children's Hospital of Orange County, California, has shared numerous interesting cases, some from exotic places during his time in the Army.

Figure 1. A 6-year-old girl who presents with fever, decreased appetite and activity, and puffy eyelids. Image: Michael Cater, MD.

In the next four articles, I will be featuring more of Mike’s cases, which may test your diagnostic ability as well as your knowledge of medical history.

Figure 2. An 8-year-old girl who presents with fever, sore throat, malaise and puffy eyelids. Image: Michael Cater, MD.

Girls present with ‘S-shaped’ swollen eyelids

Three girls, 6, 8 and 13 years of age, each presented with 5 days of fever and puffy upper eyelids (Figures 1 to 3).

Figure 3. A 13-year-old girl who presents with fever, headache, sore throat and puffy eyelids. Image: Michael Cater, MD.

When examined, the margins of their upper lids appeared in a slight sideways “S-shape” configuration.

Figure 4. An adolescent boy with exudative tonsillitis due to mononucleosis. Image: Michael Cater, MD.

The 13-year-old girl also had headache, sore throat with exudative tonsillitis, like that shown in Figure 4, and was empirically treated with amoxicillin, but she soon developed a generalized maculopapular rash, as shown in Figure 5.

Figure 5. The same adolescent boy shown in Figure 4 with a rash after receiving amoxicillin. Image: James H. Brien, DO.

The 8-year-old also had a sore throat with malaise. The 6-year-old had decreased appetite and activity but no other symptoms. Lab results are pending.

What’s your diagnosis (most likely cause)?

A. Adenovirus

B. Influenza

C. COVID-19

D. Epstein-Barr virus

Answer and discussion:

These patients have the same diagnosis but a different mix of symptoms, except for the common denominator of swelling of the upper eyelids, otherwise known as the Hoagland sign, which occurs in advance of, or simultaneously with, other early findings of Epstein-Barr virus (EBV) infectious mononucleosis (IM). Some refer to eyelid edema, but it has also been reported to result in an S-shaped curve of the upper lid margins, which implies more lacrimal gland swelling than the rest of the lid.

Figure 6. A 6-year-old girl who presents with dacryoadenitis due to Staphylococcus aureus following eye trauma, shown in December 1989. Image: James H. Brien, DO.

The lacrimal gland is located in the lateral aspect of the upper lid, and when swollen from infection (dacryoadenitis) or injury, the lateral aspect of the lid gets pushed downward, producing a characteristic sideways S-shape distortion. In the December 1989 column, I showed a dramatic example of this lid distortion due to traumatic dacryoadenitis caused by a Staphylococcus aureus infection after a penetrating injury with a pencil (Figure 6).

Figure 7. A 2-year-old boy who presents with fever and dacryoadenitis due to adenovirus. Image: James H. Brien, DO.

While other bacteria can rarely cause dacryoadenitis, most cases in children are due to viral infections and are often unilateral (Figures 7 and 8). However, in the case of EBV infection, the Hoagland sign is classically bilateral. This leads me to think that the cause of Hoagland sign is due to the direct effect of infection of both lacrimal glands with EBV, or it is EBV immune mediated.

Figure 8. A 3-year-old boy with dacryoadenitis caused by influenza. Image: James H. Brien, DO.

 

It has been described as the earliest sign of IM, and before rapid strep testing came along, this finding could be useful when deciding on empiric antimicrobial therapy in those with fever and exudative tonsillitis. Another sign of EBV IM is the characteristic maculopapular rash that occurs in about 20% of those who also receive antibiotics, most commonly amoxicillin, as shown in Figure 5.

Regarding COVID-19, Singh and colleagues published two adult cases with unilateral dacryoadenitis — one due to COVID-19 infection and the other after a COVID-19 immunization. They postulated that an immune-mediated response may be the underlying cause. The full paper can be found here.

Columnist comments:

Somehow, I got through a military residency and fellowship and 20 years in the Army Medical Corps without ever hearing of the Hoagland sign or the fact that Robert J. Hoagland, MD, (1909-2007) was a very noteworthy Army physician and subsequent civilian physician in the mid-20th century. He served in the Army Medical Corps in Europe during World War II, as well as numerous clinical and command assignments. He was known as one of the early experts on IM and subsequently, EBV. The fact that I don’t recall Dr. Hoagland should not be interpreted as a deficiency on the part of my mentors but more likely a reflection of my deteriorating memory of ALL THINGS, such as dates, events and people, (including a few relatives). If interested in knowing more, I would direct you to Dr. Hoagland’s obituary here.

I would like to thank Dr. Mike Cater for contributing the cases used in this column.

References:

• Robert Hoagland obituary. The Charlotte Observer. https://www.legacy.com/us/obituaries/charlotte/name/robert-hoagland-obituary?id=13704108. Published Oct. 2, 2007. Accessed April 12, 2024.
• Singh S, et al. Indian J Ophthalmol. 2023;doi:10.4103/IJO.IJO_30_23.

For more information:

Brien is a member of the Healio Pediatrics Peer Perspective Board and an adjunct professor of pediatric infectious diseases at McLane Children's Hospital, Baylor Scott & White Health, in Temple, Texas. He can be reached at jhbrien@aol.com.