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ARTICLE
Year : 1956  |  Volume : 4  |  Issue : 3  |  Page : 45-52

Eye in histoplasmosis


Ophthalmic Dept., King Edward VII Memorial Hospital, Bombay, India

Date of Web Publication10-May-2008

Correspondence Address:
B T Maskati
Ophthalmic Dept., King Edward VII Memorial Hospital, Bombay
India
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Source of Support: None, Conflict of Interest: None


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How to cite this article:
Maskati B T. Eye in histoplasmosis. Indian J Ophthalmol 1956;4:45-52

How to cite this URL:
Maskati B T. Eye in histoplasmosis. Indian J Ophthalmol [serial online] 1956 [cited 2020 Aug 6];4:45-52. Available from: http://www.ijo.in/text.asp?1956/4/3/45/40747

Histoplasmosis has not been commonly recognised in this country and con­sequently has attracted little attention. A brief account of it may therefore be helpful as an introduction to the case reports which follow:­

Darling (1906) discovered histoplasmosis when he was actually looking for the organism which Leishman and Donovan (1903) had then just recently described independently as the cause of Kala-azar. Darling examined every enlarged spleen which he found at necropsy in Panama Canal Zone, and although he found no Leishmaniae at this time, he collected three cases in which an encapsulated intracel­lular organism was present. He believed that this organism was a protozoon, and he gave it the name by which it is now generally known. De-Rocha-Lima (1913) drew attention to the morphological resemblance between Darling's Histoplasma Capsulatum and cryptococcus farciminosus now commonly known as histoplasma farciminosus, and suggested that histoplasma capsulatum might belong to the fungal group of Blastomycosis. The fungal nature of this organism was proved when De-Monbreum (1934) succeeded in cultivating it. Since then the disease has been recognised in many parts of the world.


  Mycology Top


The fungus exists in two forms:­

(1). A mycelial phase which is found when it is existing as a saprophyte, or if it is cultured at a temperature of 22ºC.

(2). A yeast like phase which occurs when it is living as a parasite or if it is grown on enriched media at 37º C.

Histoplasma capsulatum is a small 2 to 4µ, budding, oval, yeast like organism which in the body appears to grow exclusively on the cytoplasm of endothelial and mononuclear cells. The organisms are about the size of Leishmania Donovan but lack the central nuclear material. They can be demonstrated in tissue sections by Gram's stain, more clearly by Giemsa's method. [Figure - 1]


  Cultural Characteristic Top


The tissue stage of histoplasma capsulatum can be grown on blood agar slants at 37º C if the tubes are sealed after inoculation. The colonies which are yeast like, smooth and white to cream in colour closely resemble the colonies of staphylococcus albus. Microscopically the growth is composed of small, oval, single. building cells 2 x 4 U in size. [Figure - 2]

A filamentous growth occurs on Sabauroud's glucose agar at room temperature. The growth is at first cottony and white but gradually becomes buff to brown with age.

Histoplasma capsulatum is killed at 55° C for 15 minutes and l to 2 per cent formalin in 24 hours. No endo or exotoxins have been demonstrated. The filtrates of broth cultures of the mycelial phase of histoplasma capsulatum contain sub­stances which may be used to detect hypersensitivity to the organism. This material known as histoplasmin is prepared by growing the filamentous culture for 2-4 months in a synthetic medium. The yeast phase and histoplasmin can be used as antigens in a complement fixation test with sera from animals and infected humans.

Dubois et al (1952) have suggested that at least some cases of the disease occuring in Africa are caused by an organism which they have named histoplasma Duboisu and which differs from the usual strains of histoplasma cansulatum in the presence of uncommonly large yeast like forms in the infected tissues. These large forms measure 13 by 10 while the histoplasma capsulatum measures about 3-4 by 2


  Epidemiology Top


The fungus hay been isolated from the soil in many areas, and some twenty species of animals both wild and domestic have been found to harbour the parasite, the bulk of natural infection being found in dogs, cats and rats; it has also been found in high proportion of skunks and opossums but only a small number of these animals have been examined. Birds have not been found infected with histoplasma, and seem to be highly resistant to it, though the fungus can be found in profusion in their droppings and in the litter of poultry houses.

Although there is no evidence of case to case transfer of infection in man, there is experimental evidence that infections can be transmitted naturally from dog to dog. It is possible that 'human infection has resulted from contact with infected animals in cases where the disease in man has occurred in households where pets or house-mice are also infected, however it may well be that in such cases man and beast have been infected from a common source such as dust, since the chief portal of entry is thought to be the respiratory tract, but the disseminated form may originate in some part of the gastrointestinal tract. Primary skin lesions also occur but they are uncommon. Special precautions seem necessary in labo­ratories as already 41 cases of infection, with clinical illness have been reported amongst laboratory workers who had been handling histoplasma capsulatum.

A number of sma'1 epidemics have occurred on farms in the United States. Exploring caves, and playing in hollow trees have been linked to other outbreaks. Saw dust, decaying wood, and excreta of animals and birds have been incriminated as the source of infection in some outbreaks. They possibly provide the moist environment necessary for growth of the fungus, while yet allowing the infective material to dry out enough to be carried on air currents, and so to enter the lungs of those exposed.

The incubation period is not known with certainty but is thought usually to be from 4-6 weeks, with a range of from 2 weeks to 3 months.


  Incidence Top


Histoplasmosis is known to occur in many parts of the world: its geographical distribution is far from completely worked out and may prove to be world-wide. In parts of the great endemic areas of the Mississippi, Missouri and Ohio Valleys, as many as 80 or more persons in every hundred showed evidence of post sub­clinical infection in the form of a positive histoplasmin skin reaction; it has been estimated that 20-30 million people in U.S.A. have histoplasmic infection. Outside United States infection is said to be most prevalent in Mexico and Central America; an increasing number of cases is being recognised in Canada, South America, Africa, the East Indies, the Pacific Islands and Australia. Sporadic cases have been found in countries bordering the Meditaranean and the few European cases appear to have been confined to that area.

As regards India, Wahi (1952) examined 957 children for histoplasmin sensiti­vity and detected 19 reactors, i.e. 0.5%.

Taneja, Kalra, Waller and Sachdeva (1955) examined 962 healthy soldiers coming from all parts of India and found 9 positive reactors to histoplasmin. All the nine showed pulmonary calcification, peribronchial thickening and hilar densities.

Edwards (1956) examined 2.341 children at Ramgarh, Darjeeling, Kelur, Sakthikulangara. Only in the Darjeeling area in the Himalayas he found 0.2% of positive reactors.

Kalra, Borcar and Rebello (1957) isolated a strain of the fungus from the soil around the entrance of a bandicoot burrow, but could not isolate the same from rodents. They isolated another strain from the sputum of a patient which was identified culturally. Roentgenography revealed peribronchial thickening in the lungs, although there were no clinical signs of pulmonary involvement.

Panja and Sen (1954) appear to be tIe first to have discovered clinically the first two cases of histoplasmosis in India. In their cases, the skin and viscera were involved. Biopsy revealed typical intracellular parasites although they could not be verified culturally or by animal experimentation.


  Pathology Top


The fungus invades and multiplies within the reticulo-endothelial cells and in the disseminated form it may be found throughout the body or confined to a single organ, the suprarenal may be the principle or only organ involved. In acute disseminated infection with fatal termination, intra cellular organisms may usually be found post-mortem in stained sections of tissues from lungs, liver, spleen and suprarenal glands. The gastrointestinal tract is often affected and bone marrow invariably. The organism produces greyish white nodules, usually multiple varying in diameter from 2-3 mm. upto several centimeters.

In the benign pulmonary infections, multiple, small, discrete, fibrotic nodules may be found in any part of the lungs, and early enlargement of the tracheo­bronchial and hilar lymphatic glands is usual. The central portions of the nodules become caseous and later calcify: these residual lesions are often seen in routine radiograph taken months or years after the infection occurred.


  Clinical Features Top


Both sexes are susceptible at all ages, the highest incidence being either during the first year of life or in the later adult years. Amongst adults males are infected seven times as frequently as females.

(I) Disseminated Histoplasmosis:

This may be an acute and rapidly fatal illness, and this form is most common in infants, in the aged, or in those debilitated by tuberculosis or malignant disease. More commonly it runs a subacute course extending over many months.

Common early features are debility, loss of weight, low grade fever, sweating, joint pains, and muscle pains, abdominal discomfort and diarrhoea, leucopenia and progressive anaemia are almost invariable and enlargement of liver and spleen are usually found. Involvement of suprarenal may destroy so much glandular tissue that Addison's disease results, and histoplasmosis should always be excluded when such a diagnosis is made.

If the infection spreads to the lungs it will usually give rise to pneumonitis with an abrupt onset accompanied by fever 103° - 104° F. but seldom any clinical feature to distinguish it from viral pneumonia.

(ii) Primary Pulmonary Histoplasmosis

This from is very often asymptomatic, it may cause mild catarrhal symptoms and malaise, and suggest influenza or bronchitis. Spontaneous recovery is the rule and the disease is seldom recognised. It may be months or years before the residual lesions are seen in a radiograph, as the examination is nearly always made either as a routine or for some other conditions.


  Laboratory Top


Histoplasmin Skin Test : The histoplasmin skin reaction develops within a few weeks of infection. 0.1 c.c. of 1 : 1000 dilution of a standardised histoplasmin is injected intracutaneously. The reaction is read 48-72 hours in the same way as for tuberculin test. A positive test is found not only during the clinical stage of the disease but in many healthy persons living in endemic areas. As such reactors have an unusually large incidence of pulmonary calcification, it seems probable that a past infection with histoplasma has healed spontaneously without causing any recognisable illness.

Complement fixation test : In acute infection complement fixing bodies appear in the blood towards the end of the third week of the disease and increase during its course gradually diminishing as recovery sets in. In chronic pulmonary infec­tion they may persist for many years.

Culture : If the infection is scanty, culture can be made from infective material such as blood. bone marrow or sputum, and they should be observed for 6 - 8 weeks before they may be considered negative.

Biopsy : When biopsy is possible sections of enlarged lymph nodes or tissues from superficial lesions or splenic or hepatic puncture may show endothelial cells packed with histoplasma capsulatum.


  Differential Diagnosis Top


When lung is involved during its course it should be differentiated from chronic pulmonary tuberculosis, bronchiectasis, bronchogenic carcinoma. When the infec­tion is confined to the mediastinal lymph nodes it must be differentiated from Boeck's sarcoid or lymphoma.

More than one quarter of the fatal illnesses occur in infants under one year of age. In these the disease is always in disseminated form and it has been found that over two-thirds of disseminated histoplamosis have a fatal termination.

The majority of benign asymptomatic infections are overcome without any noticeable disturbance of health.


  Treatment Top


Most of the reported antibiotics and sulfonamides have been tried and they have been reported as ineffective. The use of cortisone should be avoided. Ethylvanillate received favourable reports in the beginning but later treatments failed to confirm its value. Stilbamidine, and recently 2-hydroxy stilbamidine have shown favourable influence on the course of the disease. Nystatin seems promising but is still under trial. MRD-112 has also marked antifungal action with low toxicity and shows good clinical improvement.


  Case Reports Top


Case I

Male aged 32 years, Bohra by caste, came for defective vision right eye. About the full duration, the patient was unaware but discovered the defective vision in the eye one year back. External examination of both the eyes was normal.

Left eye vision was 6/6, no refractive error. Media were clear. Nothing abnormal was found in the fundus oculi.

Right eye vision was reduced to finger counting at 10 feet. Refraction deter­mined by skiascopy was +2.25 in both axis but no improvement in vision was possible with glasses. Media were clear. Fundus oculi showed the presence of an area of central chorioretinitis. The remaining retina and retinal blood vessels appeared to be normal. [Figure - 3].

Case II

Male, 30 years. Bohra by caste, came for defective vision in the left eye. The patient was not aware of the defective vision in the left eye. Right eye vision was 6/6. External examination of both eyes - normal. Fundus and media of the right eye were normal.

Left eye vision was reduced to finger counting at 20 feet. Media were clear. Fundus oculi showed a patch of central chorioretinitis. [Figure - 4].


  Investigations Top


In both the cases the results of investigations were identical.

General clinical examination of all the systems and examination of blood and urine were non-contributory. No visible foci of sepsis were detected.

Dermal tests with tuberculin, brucellin and toxoplasmin were negative. Histo­plasmin dermal reaction was strongly positive in both the cases.

X-Ray examination of the chest showed multiple calcified nodules in both the lungs. [Figure - 5],[Figure - 6].


  Discussion Top


Both these patients are from Bombay and have never left India, there is no definite history of contacts with domestic or wild animals. As to the diagnosis of histoplasmosis - pulmonary benign asymptomatic type - there is no doubt. in view of the positive histoplasmin test which is very specific and specially in a nonendemic country, and again the typical X-ray appearance confirms the diagnosis.

Now as regards the central chorioretinitis in both these patients, the appearance is like that one finds in Toxoplasmosis, resembling a colobomatous defect. The macular area seems to be specially involved. the patch of chorioretinitis is well circumscribed with an atrophic central area. The border is pigmented and the pigment also extends in the centre. However, there is no way of proving beyond all reasonable doubt that they are the result of histoplasmosis. It is fair and logical to conjecture that systemic disease like histoplasmosis, which spares no organ in the body in its affection could have caused this eye lesion. To our knowledge, so far no case has yet been described of any eye lesion in cases of histo­plasmosis.

The eyes are said to be the windows of the body and our cases presented here prove once again the truth of this statement. It is through these windows we were able to unmask two cases of histoplasmosis with ocular manifestations.


  Summary Top


Case reports of two cases of histoplasmosis are given in which ocular signs (uniocular central choroiditis) have been observed for the first time.

Epidemiology, incidence, pathology and clinical manifestations are described.[12]

 
  References Top

1.
Darling, S. 1. (1906) J.A.M.A. 46, 1283.  Back to cited text no. 1
    
2.
da Rocha-Lima. H. (1913) Zentralbl. F. Bakt. 67, 233.   Back to cited text no. 2
    
3.
De Monbreun, W. A. (1934) Am. J. Trop. Med. 14, 93.   Back to cited text no. 3
    
4.
Donovan, C. (1903), Brit. M. J. 11, 79.  Back to cited text no. 4
    
5.
Dubois, A.. Janssens. P. G., Brutsaert. P. and Vanbreuseghem, R, (1952), Am. Soc. beige Med. Trc.p. 23, 569 (as quoted in 10).  Back to cited text no. 5
    
6.
Edwards. P. Q., Geser, A. G., Kjolbyc, E. H., Meijer, J. and Christensen, O. M., (1956), Amer. J. Trop. Med. Hyg. 5, 224.  Back to cited text no. 6
    
7.
Kalra, S. L., Borcar. M. D. S. and Rebello. E. R. F. (1957), Indian J, Med, Sci, 11, 496.  Back to cited text no. 7
    
8.
Leishman, W. B. (1903); Brit. M. J. I; 1252.  Back to cited text no. 8
    
9.
Panja. G., Seri, S. (1945), J. Indian Med. Assn. 23, 257.   Back to cited text no. 9
    
10.
Symmers, W. St. C. (1956) Brit. M. J. 11, 786.  Back to cited text no. 10
    
11.
Taneja, B. L., Kalra, S. L., Waller, S. O., and Sachdeva, I,. D. (1955) Army Med. Corps. J. 11, 149.  Back to cited text no. 11
    
12.
Wahi, P. N. (1952). Agra Univ. J. Res. 1, 205.  Back to cited text no. 12
    


    Figures

  [Figure - 1], [Figure - 2], [Figure - 3], [Figure - 4], [Figure - 5], [Figure - 6]



 

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Mycology
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