SHAPU - Seasonal Hyperacute Pan-Uveitis

From EyeWiki

This page was enrolled in the International Ophthalmologists contest.


SHAPU Patients presenting with similar clinical features at a specific time of the year.

Disease Entity

Seasonal hyperacute panuveitis (SHAPU)is a mysterious disease seen and reported only from Nepal since 1975.An important cause of unilateral childhood blindness. It is the most devastating intraocular inflammatory disease which leads to loss of sight within a week and, in many cases disfigurement later. Although initially presented as case report at a Nepal Prevention of Blindness meeting in 1978 and reported in national journals [1], detailed description of the condition including epidemiology, serology and histology appeared first in an international  peer reviewed journal based on several years of work at the Department of Ophthalmology, Institute of Medicine [2]  in 1984 as a severe form of panuveitis.

Disease

Seasonal Hyperacute Panuveitis (SHAPU) is a unique, most rapidly destructive intra-ocular inflammatory disease .It occurs in two year cycles in odd years since 1975.[1] It occurs in epidemic form beginning with end of monsoon ( August –September) and usually ending with peaking of winter in December-January.[1][2]Affecting children predominantly the disease is almost always unilateral with rapid and profound loss of vision.[1][2][3][4][5]

In fact two thirds of them present with a blind eye and the rest lose vision rapidly.

Within a few days the eye becomes soft with shallowing of anterior chamber which has been called "Malignant Hypotension".[1][4]  Hypopyon, fibrinous exudates in anterior chamber, a difficult to dilate pupil and inability to visualize retina because of massive exudation into vitreous producing a "White pupillary reflex in Red eye" with little or no pain are other characteristic features of the disease.

To distinguish it from hitherto reported eye diseases, Upadhyay et al,[4]  and Rai et al,[5] called it Seasonal Hyper-acute Panuveitis (SHAPU) in view of its seasonal occurrence, devastating rapidity of progression of the disease, no history of intraocular surgery or trauma to the eye  and absence of bacteria and fungi  in aqueous and vitreous aspirates  to distinguish it from endophthalmitis.[1]

Etiology

Most data on etiology rely solely on contact history with a suspected agent (moths) and there is evidence suggesting that the disease is due to exposure to possible toxins. But with more cases – not all agree to the existing knowledge.

Unilateral involvement with white pupil. Patient has minimal symptoms.

While etiopathogenesis is still debated, the data from researchers do agree on some key peculiarities.SHAPU usually affects one eye, has a cyclic epidemic pattern occurring during the period of the end of monsoon (August-September) and the beginning of severe winter (December-January). The recent analysis predicts that since first being identified in 1975, epidemics have occurred every odd year. With that, the year 2017 also falls into a perfect timeline for another major epidemic.

While this remains unexplained , the most common cause of  panuveitis among pediatric patients in Nepal is reported to be  SHAPU (27,7%), followed far behind by Toxoplasmosis(9.3%).[6]

Most reported cases of SHAPU have occurred during the period of end of monsoon(August-September) and beginning of severe winter (December-January).[3]Although sporadic cases have been seen until about March, very few have been reported before August. This high prevalence of SHAPU in children is, on its own, an important reason to undertake further research from public health perspectives to protect eyes of children. 

The disease still remains a mystery with no hard evidence of its source. So far, management protocol or treatment has been limited.  SHAPU continues to delude - and continues be to most devastating inflammatory eye disease rendering eye functionless within a week.

Risk Factors

In the first comprehensive report of SHAPU, described, a series of animal experiments  in which the authors  exposed guinea pigs and rabbits to live  Megalopygidae, Arctiidae, and Noctuidae moths in a closed room in four sets of experimental designs described elsewhere. Lesions could not be reproduced in any of the experiments. They concluded that, if moth was indeed either an inducing or transmitting agent, possibly the moths used by them in this experiment were not the type to produce the disease  or that the rabbits and guinea pigs were not susceptible hosts and recommended continued vigilance and further studies.

Based on cases seen since the epidemic was first observed and also recent studies, most cases have been reported from subtropical (1,000 to 2,000 meters), temperate (2,000 to 3,000 meters) and subalpine (3,000 to 6,000 meters) regions of eastern, central and western Nepal. Very few cases have been reported from the tropical plains of Nepal.

Geographically,two interesting features requiring further explanation include its localization to certain climatic zones of Nepal while such climatic zones exist in many countries along the Hindukush mountains (Afganisthan, Pakistan, India, Nepal,Bhutan, Bangladesh, Myanmar and China).

Reports continued to be published linking moths to SHAPU interspersed with large scale exposure to few exposures. Moths therefore remain legendary suspects.  

Pathophysiology

Affecting children predominantly, the disease is almost always unilateral with rapid and profound loss of vision.[1][2][3][4][5]Starting as a red-eye with little or no pain, this quickly turns into something more frightening within days. Hypopyon, fibrinous exudates in the anterior chamber, a non-dilating pupil with massive exudation into vitreous start manifesting and eyes then become soft –resulting in "Malignant Hypotony".[2][3]

“White pupillary reflex in Red eye" with little or no pain remains the hallmark in most of the cases. No gender predilection is reported in any of the series. No statistically significant difference has been noted in regard to laterality among either eye.

Youngest in the series by Upadhyay et al [3] has been a 9-month-old infant but can range up to 45 years. It has been reported from the midwestern, central and eastern belt of hilly regions of Nepal.

Earlier circumstantial evidence of exposure/contact with moths has been subsequently reinforced by clinical observation of intrastromal follicles in the cornea in some cases. However, many further cases failed to demonstrate similar finding. This has caused the origins to be questioned again – making the pathogenesis ever more enigmatic.

Oscillating between non-infective and infective origin, all cases in early reports were treated either with antibiotics, antivirals, immunosuppressive with uniformly poor results[1][3] Early interventional vitrectomy has shown promising outcomes.[5]

Primary prevention

Currently, the only primary prevention is to avoid contact with moths during the seaons of epidemicity.

Definition of a SHAPU epidemic:

The disease reported only from Nepal occurring in two-year cycles in odd years since 1975.[3]It occurs in epidemic form beginning with endof monsoon (August – September) and usually ending with height of winter in December-January[3][4]Therefore, this is a difficult question to answer as random clusters mimicking an outbreak may occur during the above time frame or inbetween. With such a low background incidence, even one or two extra events during a short time frame can raise concerns but may turn out not to be significant and may be followed by an unusually long period with no cases so that the frequency over a longer time frame may be within acceptable limits. 

Physical examination

Seasonality, appearance in odd years, hyper-acute presentation in otherwise healthy individuals, without history of eye surgery or trauma, staring white pupil in a red eye (contrast this to more conventional white pupil in a white eye), and a shallow anterior chamber in a soft eye without history of previous surgery or eyedisease are features not described for any other ocular entity.

A Typical case of SHAPU - A child presenting of unilateral nonpainful red eye with while pupil

Clinical Features

Most the clinical symptoms and signs of SHAPU are non-specific.

Symptoms

  • Sudden onset of redness with minimal pain*
  • White pupillary reflex (leukocoria) in a red eye *
  • Unilateral involvement
  • Decreased vision

Signs

  • Circumciliary congestion
  • Leukocoria
  • Fibrinoid anterior chamber reaction
  • Hypopyon
  • Shallow Anterior chamber
  • Collection of fibrinoid exudates in the crypts of muddy iris
  • Decreased intraocular pressure (malignant hypotension)*
  • Retinal assessment is difficult


Footnote - * Hallmark in most cases

Clinical diagnosis

Clinical case description and identification of SHAPU

Major

  1. White pupillary reflex in Red eye
  2. Little or no pain
  3. Almost always unilateral
  4. Rapid and profound loss of vision.


Minor

  1. Malignant Hypotension
  2. Children predominantly
  3. Hypopyon, fibrinous exudates in anterior chamber
  4. A difficult to dilate pupil and inability to visualize retina


SUSPECTED case (1 Major with 1 Minor OR 2 Major criteria)
Major:  

  1. Almost always unilateral
  2. Whitepupillary reflex in Red eye


Minor:   

  1. Children predominantly 


PROBABLE case (Major ≥2 with at least 1 Minor criteria  OR 1  Major with 3 Minor criteria)

Major

  1. White pupillary reflex in Red eye
  2. Little or no pain
  3. Almost always unilateral


Minor

  1. Children predominantly
  2. Hypopyon, fibrinous exudates in anterior chamber.
  3. A difficult to dilate pupil and inability to visualize retina 


CONFIRMED  Case (Cases matching all the major and minor criteria)

Major:  

  1. White pupillary reflex in Red eye
  2. Little or no pain
  3. Almost always unilateral
  4. Rapid and profound loss of vision                                 


Minor:

  1. Malignant Hypotension
  2. Children predominantly
  3. Hypopyon, fibrinous exudates in anterior chamber.
  4. A difficult to dilate pupil and inability to visualize retina 

Diagnostic procedures

Outflow of microbiological investigation for ocular fluid sample

Laboratory test

Specimen collection

  • Specimens-vitreous fluid, aqueous fluid, conjunctival swab, blood
  • Specimens should be collected by ophthalmologists in the operation theatre maintaining the sterility.
  • Both diluted and undiluted vitreous fluid should be collected in a sterile syringe.
  • The conjunctival swab should also be collected from both eyes. It serves as a control when comparing with the ocular fluid samples
  • Blood sample is collected to rule out endogenous endophthalmitis

Specimen transportation

  • Specimens are inoculated in the culture medium - mainly for bacterial and fungal isolation. The inoculated media and slides prepared should be immediately transported to the laboratory.
  • OR, the samples are directly transported to the laboratory for culture an staining.
  • Some amount of sample should be preserved for viral PCR and future use at -80°C

Procedure

  • Each of the samples(except the blood) should be inoculated in Brain heart infusion broth, Chocolate agar and Robertson’s cooked meat media for bacterial culture and fungal culture. Incubation should be done at 37°C for atleast 24-48hours.
  • Chocolate agar is for the identification of Haemophilus influenza and Streptococcus pneumonia.
  • Subculture from brain heart infusion broth should be done in Chocolate agar, Blood agar and Mac Conkey agar and incubated at 37°C for 24-48 hours for isolation of other aerobic bacteria.
  • Subculture from brain heart infusion broth should be done in Sabouraud’s dextrose agar and incubated at 25°C and 37°C over a period of 3 weeks for fungal culture.
  • Robertson’s cooked meat media is for anaerobic culture. Subculture should be done in Chocolate agar,Blood agar and Mac Conkey agar and incubated at 37°C for 48-72 hours in an anaerobic jar.
  • 2-3 smears should be prepared from each sample (except the blood) for gram staining and giemsa staining.
  • Blood sample should be inoculated into Brain heart infusion broth and incubated at 37°C. Subculture should be done in Chocolate agar, Blood agar, Mac Conkey agar after 24 hours and/or after appearance of turbidity.
  • Viral PCR should be done and sequencing of the preserved sample should be done.

Identification

Identification of the bacteria and fungi should be done based on their morphology and various biochemical tests

Interpretation (for bacterial and fungal growth)

Vitreous fluid

any growth is significant if growth is present in both diluted and undiluted sample.

Note – growth for any sample is considered significant if same organism grow in 2 solid or 1 liquid and 1solid medium.

Aqueous fluid

Any growth is significant if is present in aqueous fluid but the organism grown in aqueous fluid should be same as that grown in vitreous for it to be the causative agent of  SHAPU.

If growth is present in aqueous fluid but not in vitreous, that may be other pathology of eye.

Conjuntival swab

If growth of the organism in the conjunctival swab of the affected eye is same as that of the normal eye, it indicates that the organism is a normal flora. But if organism grown in conjuctival swab culture and vitreous fluid is the same, the flora itself is the pathogen. For the confirmation, a repeat conjunctival swab and vitreous tap should be done (if possible) to rule out contamination during the procedure

Blood culture

Growth of same organism in blood and vitreous fluid culture indicates that the cause of panuveitis is endogenous or it is a condition of secondary bacteremia.

Differential diagnosis

The differential diagnosis therefore may include a range of entities .

Infectious conditions

  • Endogenous endophthalmitis
  • Exogenous endophthalmitis
  • Herpetic retinitis
  • Tuberculosis
  • Syphilis
  • Fungal infection in drug users
  • HIV retinopathy
  • Toxoplasmosis

Immunological conditions

  • Sarcoidosis
  • Multipleevanescent white dot syndrome (MEWDS)
  • Behcet’s disease

Management

The patients will mostly be received as emergency cases or OPD cases. A team of concerned doctors will do a thorough history taking and perform the detailed ocular evaluation. Systemic examinations will also be performed to rule out any systemic associations.

We recommend the following hierarchy system to be established for better management of the cases.

SHAPU - Management Hierchy System

History should be take nin details and following points should be included in it:

  • Patients profile including age, sex,address (Temporary and permanent)
  • Ocular Complaint
  • Contact/Exposure history


Definition of Contact/ Exposure History:

Any person who has been exposed to or has had direct physical contact

  • To live or dead moth immediately prior to onset of the condition.
  • Possible contact with hair/follicles at work/home – e.g: de-dusting, gardening, farming
  • Past ocular medical and surgical history
  • Systemic illness/medication
  • Family and personal history
  • Treatment history


After taking a detailed history, the ocular examination should be done systemically as stated below:

Non-Invasive Evaluation:

  1. Visual Acuity
  2. Extraocular movements
  3. Periorbital region/lids and adnexal examination using slit lamp
  4. Special mentions about Conjunctiva, episclera, and sclera if any.
  5. Anterior segment examination of the cornea
    • Anterior chamber, iris, pupil, and lens. Pupillary light reflex both direct and consensual should be noted using bright torchlight. Clinical photography is mandatory for documentation
  6.  Proparacaine Hydrochloride Ophthalmic Solution USP, 0.5% shouldl be instilled in both eyes and after 30 seconds, the Intraocularpressure shouldbe taken with the help of Goldmann applanation tonometer if patient permits.
  7. Detailed fundus examination under mydriasis using eye drop Tropicamide 1% should be performed with direct ophthalmoscope, binocular indirect ophthalmoscopy with +20D lens and h +90D lens whenever indicated and feasible.In cases with a poor fundal view, ocular ultrasonography should be done and the findings documented in a print.
  8. In cases with some fundal view,  OCT can be used as a noninvasive method for microscopic anatomical evaluation.


General treatment

Medical therapy

For any suspicious case of SHAPU topical antibiotics Tobramycin can be started 4 hourly in affected eye and case should be referred promptly.

Patients will be thoroughly examined and treatment can be started as follows if diagnosed as SHAPU or presumed SHAPU:

Moxifloxacin 1 hrly, Prednisolone acetate 1 hrly,Atropine TDS, Ceftriaxone intravenous 50 to 75 mg/kg IV or IM once a day or adults 1-2 g iv or im OD or BD ,Methylpredinisolone intravenous ( <20 kg=500mg OD, 20-40kg=125mg QID or 250mg BD, > 40kg=250mg QID or 500mg BD)for upto 3 days and followed by oral steroids ( 1-2mg per kg body weight) forupto 4-6 weeks depending on clinical condition

Surgery

All cases should undergo core vitrectomy with diagnostic vitreous tap within 24 hours of presentation.

Required sample volume is 2 ml of which 1 ml should be dry sample (undiluted) and 1 ml can be mixed with saline from infusion (diluted).

Eye should be painted and draped as regular preparation for vitrectomy. Three ports should be made and infusion placed without turning it on. Sample should be collected using 1 ml syringe with 26 gauge needle. First dry sample should be collected directly from the sclerotomy made for vitrectomy approx. 1 ml if possible without runninginfusion.

Then infusion should be turned on and cutter used to cut anterior vitreous. Second sample should be then collected from the vitreous cutter tubing using 1 ml syringe.

If lensectomy/cataract surgery is reuiqred , posterior capsule sample also can be collected.

After completing of core vitrectomy, intraviteal antibiotics should be given as following:

  • Vancomycin 1.0 mg, Amikacin 400 microgram and Dexamethasone 400 microgram.
  • Repeat intravitreal after 48 hrs if no improvements with vitreous tap again, if previous sample showed failed to demonstrate any organsim or its growth.


Silicon oil can be used as per surgeons discretion.

At the end of surgery all ports should be sutured using 8/0 vicryl.

Subconjunctival  dexamethasone and vancomycin at the end of surgery.

Eye is padded at the end of surgery.

Post-operative medications will continue as started pre- operatively and it can be changed according to microbiological report of samples.


References

  1. 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 Malla O, editor Endophthalmitis probably caused by Tussock moth. Report of the Proceedings of the first National Seminar on Prevention of Blindness; 1978.
  2. 2.0 2.1 2.2 2.3 2.4 Upadhyay, MP: Eye problems of Nepalese Children (1979). In Baral, M.R. (Ed.) The child in Nepal Nepal Medical Association/International year of the Child (IYC) Seminar.
  3. 3.0 3.1 3.2 3.3 3.4 3.5 3.6 3.7 Upadhyay MP. Anterior Segment Blindness among Nepalese Children. Nepas. J. 2:69)
  4. 4.0 4.1 4.2 4.3 4.4 Upadhayay M, Rai N, Ogg J. Seasonal Hyper Acute Panuveitis in Saarikm (ed): Uveitis update. Amsterdam. Excerpta Medica. 1984.
  5. 5.0 5.1 5.2 5.3 Upadhyay M, Rai N, Ogg J, SHRESTHA B. Seasonal hyperacute panuveitis. Uveitis update. 1984:257-62.
  6. Manandhar A. Seasonal hyperacute panuveitis: an update. Current opinion in ophthalmology. 2011;22(6):496-501.
  1. Byanju R, Pradhan E, Rai S, Sapkota Y. Visual outcome of vitrectomy in seasonal hyperacute pan uveitis. 2003.
  2. Malla O. Sudden blindness in Nepalese children. Kathmandu Univ Med J (KUMJ). 2005;3(1):4-5.
  3. Shrestha E. A profile and treatment outcome of seasonal hyper-acute panuveitis. Nepalese Journal of Ophthalmology. 2010;2(1):35-8.
  4. Kathil P, Biswas J, Gopal L. Demonstration of varicella zoster virus in a case of presumed seasonal hyperacute panuveitis. Indian journal of ophthalmology. 2005;53(4):270.
  5. Smits SL, Manandhar A, van Loenen FB, van Leeuwen M, Baarsma GS, Dorrestijn N, et al. High prevalence of anelloviruses in vitreous fluid of children with seasonal hyperacute panuveitis. Journal of Infectious Diseases. 2012:jis284.
  6. Upadhyay MP, Shrestha BR. SHAPU:Forty yras on- The mystery prsists. Editorial . Nepal J Ophthalmol 2017; 9(17).