“For most diagnoses all that is needed is an ounce of knowl-edge, an ounce of intelligence and a pound of thoroughness.”
This Arabic proverb found in the Lancet (1951) couldn’t be truer for a team of researchers from the Jawaharlal Institute of Postgraduate Medical Education and Research in Puducherry, India, who discovered with thorough investigations how a HIV-related eye condition presented as a part of a multisystem disorder instead.
Cytomegalovirus (CMV) retinitis is an opportunistic infection most commonly found in patients with disorders which affect the immune system, namely HIV, or blood disorders like leukemia/lymphoma, or who have undergone organ transplantations. Alarm bells rang for the study’s author, Dr. Swapnil Parchand, when a 45-year-old patient presented with CMV but was confirmed to be without HIV. This prompted him to investigate the patient through a series of tests. Together with his co-author, pathologist Dr. Adarsh Barwad, Dr. Parchand unfolded their investigations in a study report.
The patient was already diagnosed with viral retinitis but he wasn’t responding to the intravenous acyclovir treatment given before coming to see Dr. Parchand. He had been suffering from a decrease in left eye (LE) vision for the past 3 months. HIV was already ruled out by his referring ophthalmologist. The right eye (RE) had a best corrected visual acuity at 6/6 during the time he presented at the hospital while the LE had a cellular reaction 2+ with posterior subcapsular cataract.
The signs of CMV retinitis were more apparent through a LE fundoscopy which showed vitritis, optic disc pallor, retinitis patches at posterior pole, and midperiphery along the retinal vessels related with retinal hemorrhages and inflammatory vascular sheathing. A vitreous biopsy done on the LE also showed CMV retinitis.
A check into the patient’s history revealed that he had lost significant weight in the past 6 months. He also had “ash-leaf spots,” or hypopigmented macules with reticular hyperpigmentation, all over his torso and upper and lower limbs – the first of the triad of symptoms for dyskeratoris congenita (DC). His nails were also suffering from dystrophy and his lip and cheek linings had the presence of oral leukoplakia. These three symptoms pointed towards DC.
Subsequently, he underwent a full hemogram. His blood count, peripheral smear, liver and renal function tests were within normal limits. Through flow cytometry and fluorescence in situ hybridization, they discovered the telomerase length in his peripheral white blood cells was below the first percentile, confirming the patient had DC. They had already ruled out other diseases like HIV, hepatitis B and hepatitis C and venereal disease. Chest imaging showed no issues with pulmonary functions. They’d also ruled out nasopharyngeal and laryngeal carcinoma.
However, the doctors discovered asymmetric thickening of the pylorus area in his abdomen through contrast-enhanced computer tomography, along with multiple polyps in the stomach after upper GI endoscopy with thickening antropyloric walls. Subsequent biopsy from the lesion showed adenocarcinoma at an early stage, the study reported.
DC patients have cells that have defective telomere maintenance. Telomere maintenance has its importance in indicating a person’s disposition towards aging and cancer. These short telomeres obstruct the process of optimal cell replication
to the extent of compromising cell integrity. Over a period of time, this compromised replication of cells will lead to stem cell exhaustion and failure in tissues. Patients with this disorder face more risks with immunological and hematological disruptions, fibrosis of the lungs, malignancies and eventually, infections.
The diagnosis usually banks upon the triad of symptoms found (skin hyperpigmentation, nail dystrophy and leukoplakia) along with bone marrow failure. Physicians must also take into account the multisystem characteristics of the disease that encompasses developmental delay, pulmonary disease, periodontal disease, epiphora, premature hair graying or loss (seen in this case study’s patient), and development of malignant lesions.
The researchers recommended to observe at least two of the four major features of DC and that at least two of the multisystem features should be present in order to make a correct clinical diagnosis.
Differential diagnosis of dermatologic manifestations in DC cases, which may be similar to other skin issues, should be noted due to a wide spectrum of diseases. This applies to hematological disorders in DC cases as well. It is interesting to note that the patient in the case study had normal blood counts and peripheral blood smear, but he had low CD4 percentage in his white blood cells with a compromised CD4/CD8 ratio.
Nearly 70% of DC patients diagnosed as malignant die before the age of 30. Thus, it was remarkable that this patient was undiagnosed until the age of 45, when his diagnosis for CMV retinitis uncovered the core multisystem disorders.
Eventually, the patient went through a laparoscopic D2 subtotal gastrectomy. They also treated his CMV retinitis with oral valganciclovir. His retinitis lesion healed, albeit with scarring in the left eye. The right eye remained unchanged. The patient had follow-ups with a gastroenterologist, hematologist and ophthalmologist, and his progress was reported to be fine after a year of follow-ups.
Retina specialist Dr. Alay Banker, director of Banker’s Retina Clinic and Laser Centre in Ahmedabad, India related to this case study with his own experience: “Interestingly, I’ve seen healthy patients who have received intravitreal steroid injections or implants develop localized immunosuppression which gives way for opportunistic infections to develop.”
He also highlighted a recent retinitis related observation. “In India, we’re seeing more vitreal retinitis in young, healthy, immune-competent patients. Some of them develop acute retinal necrosis. So, whenever we see them develop CMV retinitis, we should investigate to rule out various viral infections and possible multisystem disorders,” said Dr. Banker.
He also advised doctors treating CMV retinitis patients with oral anti-CMV retinitis medication to supplement their treatment with intravitreal ganciclovir or cidofovir injections as intravitreal injections are direct and could supplement the oral medication’s effectiveness.
Editor’s Note: Dr. Banker was generous enough to contribute on this story, but he was not a participant of the mentioned study.
Reference:
Parchand S, Barwad A. Cytomegalovirus Retinitis as a Presenting Feature of Multisystem Disorder: Dyskeratosis Congenita. Middle East Afr J Ophthalmol. 2017;24(4):219-221.
