History: A 33-year-old white female presented with a chief complaint of a ‘bump’ on her right medial eyelid that appeared four days prior to presentation, associated with general lid swelling. She had been water-skiing one week prior to the appearance of the ‘bump’, and had fallen and hit her face in the water. She denied any other history of trauma to her face, recent sinusitis, fever, diplopia or pain. Her past medical history was significant for cervical cancer, and past surgical history included a leep biopsy and tonsillectomy. She was not on any medications, and did not smoke or drink alcohol.
Exam:
The patient was healthy appearing, alert and oriented. Her visual acuity without correction was 20/20 OU. Confrontation visual fields were full to finger counting OU. Hertel exophthalmometer measurements were 16mm on the right and 15mm on the left at a base of 100. Her pupils were equal, reactive without a relative afferent pupillary defect. External exam revealed a firm nodule located in the medial aspect of the right upper lid that was slightly tender to palpation. (Figure 1-3) Slit lamp exam and dilated funduscopic exam were within normal limits. Intraocular pressures were 17mm Hg OU.
Figure 1: Patient with fullness right upper lid with nodule.
Figure 2: Right upper eyelid lesion noted in supero-nasal quadrant of orbit.
Figure 3: Note fullness of right upper eyelid with generalized edema.
Differential Diagnosis:
Based on the clinical presentation, the differential diagnosis includes the following: a sinus mucocele given the location of the mass. A mucocele arises from primary obstruction of a paranasal sinus, most commonly the frontal or ethmoid sinus, and presents as a mass in the superonasal orbit. A ruptured dermoid cyst can be considered given the sudden onset of the lesion following trauma. Rupture of a dermoid cyst after trauma incites an acute inflammatory reaction causing an abrupt presentation of a subcutaneous inflammatory lesion. An orbital abscess is a possibility as it can present as an acute localized mass, but usually will be associated with overlying skin erythema and pain. Metastatic disease can also present as a lesion in the orbit, and our patient has a past medical history of cervical cancer. Other entities in the differential include a primary malignancy, inflammatory pseudotumor, and sarcoidosis.
Clinical Course:
Standardized echography and orbital computed tomography were performed. The diagnostic B scan showed a well-outlined lesion in the superonasal anterior orbit that was irregularly structured and without evidence of vascularity or bony destruction. (Figure 4). Diagnostic A scan revealed variable internal reflectivity (Figure 5). This pattern was more consistent with a dermoid cyst. Dermoids can have variable reflectivity depending on their intralesional contents. In contradistinction, mucoceles tend to be low-reflective. CT scan of the orbits revealed a homogenous soft tissue density confined to the preseptal area without evidence of osseous destruction. The paranasal sinuses were unremarkable (Figure 6). These findings were also inconsistent with a diagnosis of a mucocele, in which opacified sinuses and a bony dehiscence should be evident. Also, dermoids tend to be more well-defined and of variable density, with or without a bony defect.
The next step to obtain a definitive diagnosis was surgery to excise the mass. The lesion was removed in its entirety, and submitted in formalin as a single piece measuring 15x13x8mm. It was reddish in color and rubbery in consistency. The histopathology is seen in figure 7. Two cross sections of an organism are seen surrounded by a moderate amount of eosinophilic debris. On higher power view (figure 8) it is apparent that the organism is a parasite surrounded by eosinophils and chronic inflammatory cells. A high power view of the parasite (figure 9) revealed a nematode characteristic of the genus Dirofilaria, most likely tenuis. This worm appeared to be immature based on its size, approximately 100um. The characteristic features of this nematode are the thick multilayered cuticle, prominent internal longitudinal ridges and external longitudinal ridges.
Figure 4: B Scan of lesion showing irregular structure without evidence of vascularity or bony destruction.
Figure 5: A Scan of lesion showing variable internal reflectivity.
Figure 6: CT scan of the orbits showing homogenous lesion without bony destruction or sinus disease.
Figure 7: Two cross sections of the organism surrounded by eosinophilic debris.
Figure 8: Higher power view of the organism reveals a parasite.
Figure 9: High power view of
Dirofilaria tenuis.
Following excision of the mass, the patient did well without recurrence.
Discussion:
Dirofilaria is a nematode found mostly in the southern part of the United States. The mosquito is the most common vector for the microfilariae. Humans are the end host as the nematode does not propagate in man. For an unknown reason, infection is rare in children. Of adult infections, a large percentage of cases present in the periocular area, suggesting that patients more actively seek medical attention when inflammation involves the eyes. Addario, an Italian ophthalmologist, described the first case of periocular infection by Dirofilaria in 1885.1 A variety of domestic and wild animals act as natural hosts for the filariae. D. tenuis is the most common cause of subcutaneous infections and is harbored in raccoons. D. tenuis is endemic to south Florida. Based on a study done in 1988 by Isaza and Courtney, 45% of raccoons in south Florida are infected by D. tenuis, as compared to only 6% of the raccoons in north Florida.2 Other Dirofilaria known to cause infections in humans include D. immitis, found in dogs, D. ursi in bears, D. striata in bobcats, and D. subdermata in porcupines.
The lifecycle of Dirofilaria begins with the L1 larva. A blood-sucking vector, most commonly a mosquito ingests this larva, after it feeds on the natural host. L1 then molts and travels to the thoracic muscles of the insect where it molts two more times over several weeks and becomes an L3 larva. The L3 larva is the first stage representing a worm-like structure, measuring approximately 1-2mm. L3 then migrates to the mouth of the insect and deposits on the skin of the next victim at the insect’s next meal. L3 penetrates the skin and once in the human, burrows and invades the blood or lymph vessels. L3 molts to become an L4 larva that moves to the final site, most commonly in the lung or subcutaneous tissues. In the case of Dirofilaria that propagate in humans, the males attempt to find the females, which release pheromones to attract them. If they find each other, they mate, repeat the reproductive cycle and release microfilariae, sometimes for years. Not all males will find a mate. Since D. tenuis does not propagate in humans, the life cycle ends once the L4 larva deposits at the final site.3
Signs and symptoms of the infection vary. Subcutaneous nodules can be present for weeks before causing pain. The disease may mimic lung cancer. The worm usually travels to the heart where it dies then travels to the lung and causes a reactive nodule. These lung nodules are usually asymptomatic and are found on coincidental chest x-ray. Occasionally they can cause pleuritic chest pain, cough or hemoptysis. The infection may also mimic acute arthritis if the mosquito bite is near a joint. Eye manifestations of the disease include ocular irritation secondary to an active worm present most commonly in the subconjunctiva (figure 10), but also in the anterior chamber or vitreous. The presence of systemic eosinophilia has been reported to be only 20% in periocular cases.4
Figure 10 – Subconjunctival worm.
Diagnosis of the condition is made by histopathologic identification of the nematode. The Splendore-Hoeppli Phenomenon is a characteristic pathological reaction that was first described around fungus spores by Splendore in 1908.5 This phenomenon is commonly found in parasitic infections and is a reaction to antigen which may be produced or released by living or dead organisms. The reaction consists of giant cells and eosinophilic granulomas (figure 7).
Treatment of the condition involves surgical excision of the subcutaneous nodule. If the worm is active, it needs to be extracted. Extraction of a live worm can be challenging. Immobilization of the worm using a pharmacologic barrier aids in the capture. This can be done by injecting 2% lidocaine with epinephrine into the fornix or subcutaneously, depending on the location of the worm. No systemic medication is required.
In summary, Dirofilaria tenuis is a nematode transmitted by a mosquito that has been infected by a raccoon. It matures and deposits in the subcutaneous or subconjunctival tissues causing an eosinophilic and giant cell reaction. It may cause pain or ocular irritation, but may also be asymptomatic. Treatment is by excision of the worm and surrounding reaction.
Quiz:
- Characteristic ultrasound findings of Dirofilaria that are similar to those found with a dermoid cyst include:
a. bony defects
b. variable reflectivity
c. low reflectivity
d. vascularity
- The most common vector for Dirofilaria is the:
a. horse fly
b. black fly
c. mosquito
d. tick
- Natural hosts of Dirofilaria include all of the following EXCEPT:
a. bears
b. bobcats
c. raccoons
d. squirrels
- Which stage of larvae deposits on and penetrates the skin of humans to cause infection?
a. L1
b. L2
c. L3
d. L4
- Active worms have be found in all of the following EXCEPT:
a. cornea
b. vitreous
c. anterior chamber
d. subconjunctiva
- Systemic eosinophilia has been reported to be present in approximately ____% of periocular Dirofilaria infections.
a. 5
b. 20
c. 50
d. 80
- The Splendore-Hoeppli Phenomenon is:
a. a nongranulomatous reaction consisting of lymphocytes and macrophages
b. hypertrophy of goblet cells in reaction to antigen deposited by the nematode
c. a collection of red blood cells and platelets surrounding the nematode
d. a granulomatous reaction consisting of giant cells and eosinophils
- Treatment of Dirofilaria includes all of the following EXCEPT:
a. Ivermectin
b. Excision of the subcutaneous nodule
c. Extraction of the worm
d. Suramin
- Which of the following statements regarding Dirofilaria tenuis is true?
a. The most common natural host is the bear
b. Infection in children is rare
c. D. tenuis propagates in humans
d. D. tenuis presents most commonly as an active worm in the anterior chamber
- Which of the following statements regarding Dirofilaria tenuis is false?
a. D. tenuis is endemic to south Florida
b. Systemic medication is recommended after extraction of the worm
c. Infection by D. tenuis can present as acute arthritis
d. L4 larvae of Dirofilaria most commonly deposit in the lung or subcutaneous tissue
Answers:
1. b,
2. c,
3. d,
4. c,
5. a,
6. b,
7. d,
8. a,
9. b,
10. b
References:
- Addario C. Sud. Un Nematode dell’occhio umano. Ann Ottol Clin Ocul 1885;14:135-147.
- Isaza R, Courtney C: Possible association between Dirofilaria tenuis infections in humans and its prevalence in raccoons in Florida. J Parasitol 1988;74:189-190.
- Davis BR. Filariases. Dermatologic Clinics 1989;7(2):313-321.
- Kerkenezov N. Intraocular filariasis in Australia. Br J Ophthalmol 1962;461:607-615.
- Splendore A. Sobre acultura d’uma nova especie de cogumello patholgenico. Rec Soc Sci S. Paulo 1908;3:62.
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