Fundus Changes in Incontinentia Pigmenti*

265

SIDEROSIS BULB1

29. Begle, H. E.: Perforating injuries of the eye by small steel fragments. Am. J. Ophth., 12:970-977, 1929. 30. von Hippel, E.: Ueber Siderosis und die Beziehunger zwischen siderotischer und hematogener Pigmentierung. Arch. f. Ophth., 40:123-279, 1884. 31. Vossius, A.: Ein Fall von minimalem Eisensplitter in der Linse nebst Bremerkungen iiber die Diagnose intraocularer Eisensplitter. Deutche Med. Wchnschr., 35:21-22, 1909. 32. Hirshberg, J.: Ueber die Ergebnisse der Magnetoperation in der Augenheilkunde. Arch, f. Ophth., 36 :37-98, 1890. 33. Braendstrup, P.: Two cases of temporary siderosis bulbi with spontaneous absorption without im­ pairment of function. Acta. Ophth., 22 :311-136, 1944. 34. Goulden, C.: Siderosis. Am. J. Ophth., 15 :1171-1172, 1932. 35. Rychener, R. O.: Siderosis following intralental foreign body. Am. J. Ophth., 29 :346-347, 1946. 36. Rollet, E.: Small magnetic intraocular fragments removed by electromagnet. Soc. d'ophtal. Nov., 1921. Cited in The Ophthalmic Yearbook, 20:360, 1924.

F U N D U S C H A N G E S IN I N C O N T I N E N T I A (BLOCH-SULZBERGER W O L F G A N G A.

L I E B , M.D.,

PIGMENTI*

SYNDROME)

AND D U P O N T

G U E R R Y , 111,

M.D.

Richmond, Virginia A clinical entity, characterized chiefly by ectodermal defects, was described by Bloch in 1926 and given the name incontinentia pigmenti. I n 1928, Sulzberger reported on the same case and, together with others, sug­ gested in 1938 that this was part of a syn­ drome of other familial ectodermal defects. Changes in the skin have been more often described, but defects in the eyes, hair, nails, teeth, and central nervous system have been observed. It is interesting to note that the case demonstrated in 1925 by Bloch to the Swiss Dermatological Society, that of a girl, aged one and one-half years, was first admitted to the eye clinic with a diagnosis of a glioma with secondary retinal detachment. She was referred to Blochs' dermatology clinic for the differential diagnosis of a peculiar skin pigmentation, consisting of bizarre, irregular spots over her trunk and right lower ex­ tremity. Such a condition had not previously been described in any dermatosis. T h e pig­ mentation was chocolate brown in color and had been present from birth. T h e patient was * From the Department of Ophthalmology and the Titmus Eye Foundation of the Medical College of Virgina.

also subject to a recurring exudative inflam­ matory dermatitis, which, upon healing, left similar pigmented lesions. Histologically, the changes were confined to the basal layer, where small cells with piknotic nuclei, various degrees of irregu­ larity, and hydropic changes of individual cells were noted. T h e hyperpigmentation was apparently due to chromatophores contain­ ing large amounts of fine, powdery granules of melanin situated within the upper and middle cutis. Although this clinical entity is attributed to the work of Bloch and Sulzberger, the first reference was probably made by Garrod, in 1906, who observed a "peculiar pig­ mentation of the skin in an infant." Adamson, in 1907, reported on similar cases. Franceschetti and Jadassohn, in 1954, made a thorough review of the literature and collected 73 cases of the Bloch-Sulz­ berger syndrome to which Scott, et al., in 1955, added the review on 19 more. In 1938, Sulzberger and his co-workers reported the case of a 19-year-old girl with incontinentia pigmenti who, in addition, showed changes of the lens and a calcareous opacity of the cornea together with convergent strabismus. O t h e r observers have noted ocular malfor-

266

WOLFGANG A. LIEB AND DuPONT GUERRY, III TABLE 1 OCULAR CHANGES IN INCONTINENTIA PIGMENTI (BLOCH-SULZBERGER SYNDROME)

Observer

Cases Reported

Strabismus

Lechleutner-Siemens, 1929; Pierini, et al., 1945; Heilesen, 1948; Carn­ ey, 1951; Higuchi, et al., 1952; Lieb and Guerry, 1957

5

Nystagmus

Haber, 1952

1

Blue scleras

Sulzberger and Bloom, 1948; Haber, 1952

2

Myopia

Lovemann, Fliegelmann, Weidmann, and Rein, 1952; Rein and Weidmann, 1952

1

Cataract

Sulzberger, 1938; Jaramillo, Mantesota, and Rosselot, 1948; Curth, 1949; Gasteiger, 1951; I to, 1951

5

Papillitis

Kiihling, 1949

1

Exudative chorioretinitis

Lieb and Guerry, 1956

1

Retrolental fibroplasia

Uebel, 1950; Findlay, 1952; Watanabe, 1954

3

Pseudoglioma

Bloch-Sulzberger-Franceschetti and Jadassohn, 1954; Haxthausen, 1945; Duke University, 1948

3

Optic atrophy

Moncorps-Seidlmayer, 1942;Seidlmayer-Hora, 1943; Gerard-Lapiere, 1951; and Carney, 1951

4

Metastatic ophthalmitis

Kawamura, 1954; Scott, Friedmann, Chitters, and Pepler, 1955

2

Ocular Changes

mations in conjunction with this syndrome. In reviewing the literature, we found that one of our cases differs in its ocular mani­ festations from others reported previously. Table 1 illustrates the primary ocular defects and their statistical occurrence in the litera­ ture. CASE REPORT

A four-week-old Negro infant was admitted to the ward pediatric service for evaluation and diag­ nosis of a pigmented vesicular rash present since birth and believed to be incontinentia pigmenti by the dermatologists. The infant was delivered at home by a midwife after an uneventful eightmonth gestation of a 23-year-old gravida V para IV abortiva O mother. The child cried and sucked spontaneously and had no difficulties with respira­ tion. At birth, the child was noticed to have tiny pinhead-sized vesicles on all extremities with a few similar scattered vesicular eruptions over the trunk. She was taken to her family physician, who administered penicillin intramuscularly without noticeable improvement in the lesions. At the sites of healing, deeply pigmented spots were left. The child was then hospitalized in another hospital, where several serologic tests for syphilis were run but were all reported as negative. She was then

referred to our dermatologic clinic, where the diagnosis incontinentia pigmenti was made and from here to the pediatric service for confirmation of diagnosis. Physical examination on admission showed a temperature of 99.6°F. rectally, pulse 140, respira­ tion 50. She was a well-developed, well-nourished infant in no acute distress. The physical examina­ tion was completely negative except for the re­ markable pigmentation of the skin and the eye lesions. Multiple small areas of hyperpigmentation were scattered over all extremities and, to a lesser degree, over the trunk. In some places, the pig­ mented areas were so thick as to be confluent, this being generally true over the extremities. Numerous small vesicles in several stages (fresh, drying, and healing) were scattered over this same pigmented area. Both lesions showed a predomi­ nantly linear distribution (figs. 1, 2, and 3). Examination of the eyes revealed the external eye to be essentially normal. Right ftmdus. The disc showed normal colora­ tion and sharp borders. At the temporal side, there was a small pigment sickle. The superior temporal vein was engorged and showed multiple divisions resembling a pannuslike vascularization. The in­ ferior temporal vein was equally markedly en­ gorged. Temporal to the macular area, one branch of the inferior temporal vein was markedly tortu­ ous and engorged, resembling a corkscrew in con­ figuration. The whole temporal fundus, limited

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267

Fig. 1 (Lieb and Guerry). Distribution of lesions in incontinentia pigmenti. by superior and inferior temporal veins, showed marked retinal edema which was most distinct in the area of neovascularization. The macular area showed extensive pigment changes and the foveola was covered by a kidney-shaped, whitish degenera­ tion and exudate. In the surrounding area, there were several star-shaped, whitish exudates. Above the macula in the area of neovascularization, there was a large elevated focus of whitish-yellow color. While the lower border of this area of localized exudation was sharply delimited, the other border was indifferent and diminished into hazy edema. In the edematous area all the venules showed in­ creased tortuosity with "corkscrew" changes (fig. Left fundus. Optic disc and retinal vessels, with the exception of the macular region, appeared nor­ mal. In the macular area, there was extensive edema and corkscrew vessels. No foveal reflex was observed. The arterioles showed no changes. Admission laboratory work showed a hemo­ globin of 10.2 gm. percent; white count 11,900 with 30-percent polymorphonucleocytes, 67-percent lym­ phocytes, one-percent eosinophils, one-percent basophils, and one-percent monocytes. Urinalysis was negative except for a one-plus albumen urea. Sickle

Fig. 3 (Lieb and Guerry). Confluency of lesions on lower extremities. cell preparation was negative. Blood cultures showed no growth. Films of the chest and long bones were not remarkable. Electrocardiogram re­ vealed only a sinus tachycardia. Skin biopsies from areas of pigmentation showed the following histologic findings: "A moderately acute inflammation of the epi­ dermis and upper dermis. The epithelium in a large segment shows moderate acanthosis and prolongated rete pegs. A characteristic feature is the presence of dyskeratosis associated with mel­ anin pigment. Considerable pigment in melanophores is seen in the dermis. There is also a perivascular infiltrate of lymphocytes in the upper dermis. Pathologic diagnosis: incontinentia pigmenti of leg and forearm." The patient's hospital stay was uneventful except for one temperature elevation, due to an upper respiratory infection which responded rapidly to antibiotics. She was discharged after one week's hospitalization to be followed jointly in the pediatric and dermatology out-patient clinics. DISCUSSION

Fig. 2 (Lieb and Guerry). Linear distribution of lesions on the trunk.

In 1954, after a thorough review of the then current literature, Franceschetti and Jadassohn made a distinction between two groups of "incontinentia pigmenti." The first, or Bloch-Sulzberger type, occurs almost exclusively in females and is distinguished by a splashlike pigmentation and absence of malformations. The second, or Naegeli type, is found in both sexes and is characterized by the presence of a reticular-type pigmenta­ tion in association with various malforma­ tions. There is strong evidence to support the

268

WOLFGANG A. LIEB AND DuPONT GUERRY, III

.
Fig. 4 (Lieb and Guerry). Exudative chorioretlnitis with neovascularization in incontinentia pigmenti (Bloch-Sulzberger syndrome).

theory that this is an inherited or congenital defect. Cochayne feels that the presence of the condition in uniovular twins as reported by Naegeli is good evidence that it is inborn. The fact that it was present in a father and his two children indicates that it may be inherited as a dominant characteristic. Curth's cases, and those of Philpott, et al., follow the pattern of dominant inheritance. A familial pattern is also reported by Naegeli, Sobel, Levin, Asboe-Hansen, and Kitamura, et al. It has been suggested that incontinentia

pigmenti may be the end-result of a viral infection of the mother during pregnancy. In 1950, Miller, et al., reviewed the litera­ ture with respect to congenital malforma­ tions due to dermatotrophic virus infections in gravid women. Besides rubella, the viruses of Herpes zoster, scarlatina, varicella, small­ pox, epidemic parotitis, infectious hepatitis, and poliomyelitis, may cause developmental fetal anomalies such as cataracts, glaucoma, microphthalmia, mental defects, cardiac and dental abnormalities following infection of the mother during pregnancy. Harber also

INCONTINENTLY PIGMENTI

269

emphasized the similarity in ectodermal and mesodermal defects of incontinentia pigmenti and those which result from infections with dermatotropic viruses in pregnant women. In 1954, Murrell and Lingamfelter had a case which, from the histopathologic standpoint, presented a picture compatible with a viral infection. A biopsy from a hyperkeratotic lesion showed a verrucous papilloma with a number of basophilic dyskeratoses somewhat resembling molluscum bodies, confined to the stratum comeum. The molluscumlike dyskeratosis resembled those of the Shope tumor of rabbits, suggesting the possibility of a viral etiology. The first clinical reports were limited to descriptions of the pigmentary phase and the associated developmental anomalies. Carney, in 1951, was the first to stress the initial vesicular stage which often precedes the better known, bizarre pigmentary Fig. 5 (Lieb and Guerry). Skin changes in in­ continentia pigmenti: dyskeratosis, acanthosis, and enlargement of the rete peg. Increase in clear cells and hyperpigmentation in the epidermis.

Fig. 6 (Lieb and Guerry). In­ continentia pigmenti: increase in clear cells in the epidermis with clusters of melanophores in the upper dermis.

270

WOLFGANG A. LIEB AND DuPONT GUERRY, III

changes. During the initial stages, recurrent he called "a mass in the orbit." Of this crops of inflammatory lesions, primarily group, two resembled metastatic ophthalmia; vesicles and bullae, may appear in association three, retrolental fibroplasia; and three, a with blood eosinophilia. Later, linear ver- pseudoglioma. As to the etiology of the rucous lesions develop which, in the end- fundus pathology in our cases, not having stages, give way to the typical pigmentation the advantage of histologic sections, we can by which this disease is characterized. only speculate on the pathogenesis. The recent work of Wise, demonstrating Various ectodermal and mesodermal de­ fects accompany this disorder. Findlay found fundus pathology after venous occlusion associated eye disorders in 25 percent of the from any cause, suggests the possibility that cases. In our case, the dermatologic picture some such process might be operative here, was characterized by vesiculopapular erup­ particularly since the fundus picture some­ tions distributed in linear fashion, irrespec­ what resembles that of an early angiomatotive of nerve distribution over the lower sis or even Coats' disease. Because the lesion extremities, vulvae, arms, thighs, and trunk was present bilaterally, though to a lesser ex­ with greatest concentration over the extremi­ tent on one side, we favor a congenital de­ ties. Many of the vesicles demonstrated fect. However, we cannot exclude a viral an increase of pigmentation at the base. A infection because, had such an infection oc­ few of the lesions showed a verrucous sur­ curred intrauterine, it is highly possible that the lesion could still be bilateral in occur­ face. Histologically, the skin biopsy specimen rence as, namely, the congenital cataracts presented an inflammatory infiltrate in the following a rubella infection of the mother epidermis and upper dermis with a hyper- during gestation. keratosis and acanthosis. There was a periDespite the questionable etiology, whether vascular infiltrate of moderate degree in the hereditary or original, we might be able to upper cutis. From the clinical picture and consider our ocular findings as an early or histologic sections, the diagnosis of incon- rudimental stage of a disorder which may tinentia pigmenti was substantiated. later be found in the end-stages to be The eye disorders were restricted to the resembling metastatic endophthalmitis, ret­ fundi. The changes consisted of marked rolental fibroplasia, or pseudoglioma. retinal edema, primarily between the su­ Certainly, as the problem is better under­ perior and inferior temporal vessels and stood, a revision of nomenclature will be­ extending from the temporal disc margin come a necessity. This fact has already been to the periphery. There was extensive en­ mentioned by Ashton in 1954 and Scott, gorgement of these vessels and some of the et al., in 1955. smaller venous branches showed marked SUMMARY tortuosity. Aberrant vascularization was a distinct feature, especially in the superior 1. A case of exudative chorioretinitis temporal area. In the macula, a kidney- occurring in conjunction with incontinentia shaped fatty degeneration covered the fovea. pigmenti (Bloch-Sulzerger syndrome) in Surrounding this, there was a star-shaped a Negro infant is presented with illustrations area of degeneration and exudation. Focal of the skin and fundus changes. areas of exudation with elevation completed 2. A statistical analysis of the ocular de­ the picture. This whole lesion resembled an fects accompanying this disorder has been exudative type of chorioretinitis. If there is done. a relation.to cases in the literature, these 3. Various theories of the etiology are dis­ changes appear to be most closely related to cussed. those eight cases collected by Scott, which Medical College of Virginia (19).

INCONTINENTIA PIGMENTI

271

REFERENCES

Adamson, H. G.: A circinate eruption diagnosed in India as "Dhobie itch." Brit. J. Derm., 19:199, 1907. Asboe-Hansen, G.: Bullous keratogenous and pigmentary dermatitis with blood eosinophilia in new­ born girls. Arch. Derm. & Syph., 67.152, 1953. Ashton, N.: Pathological basis of retrolental fibroplasia. Brit. J. Ophth., 38 :385, 19S4. Bloch, B.: Eigentiimliche bisher nicht beschriebene Pigmentaffection. Schweiz. med. Wschr., 7:404, 1926. Carney, R. G.: Incontinentia pigmenti: A report of five cases and a review of the literature. Arch. Derm. & Syph., 64:126, 1951. Cochayne, A. E.: Inherited abnormalities of the skin and its appendages. London, Oxford, 1933, p. 325. Curth, H. O.: Follicular atrophoderma and pseudopelade associated with chondrodystrophia calcificans congenita. J. Invest. Derm., 13:233, 1949. • : Incontinentia pigmenti in a girl aged 13 months. Arch. Derm. & Syph., 60:970, 1949. Duke University: Case report. Baltimore-Washington Derm. Soc, 13:11, 1948. Findlay, G. H.: On the pathogenesis of incontinentia pigmenti: With observations on an associated eye disturbance resembling retrolental fibroplasia. Brit. J. Derm., 64:141, 1952. Franceschetti, A., and Jadassohn, W.: A propos de l'incontinentia pigmenti, delimitation de deux syn­ dromes differents figurant sous le meme terme. Dermatologica, 108:1, 1954. Garrod, A. E.: Peculiar pigmentation of the skin of an infant. Tr. Clin. Soc. Lond., 39 :216, 1906. Gasteiger, H.: Incontinentia pigmenti. Ber. Deutsch. Ophth. Ges., 57:292, 1951. Haber, H.: The Bloch-Sulzberger syndrome (incontinentia pigmenti). Brit. J. Derm., 64:129, 1952. Haxthausen, H.: Incontinentia pigmenti. Acta derm.-venereol. (Stockh.), 25:528, 1945. Heilesen, B. J.: Incontinentia pigmenti. Acta derm.-venereol. (Stockh.), 28:544, 1948. Higuchi, K., Urabe, H.: Hirohaka, T., and Hirata, T.: Cited by Kitamura: Hihu-to-Hitsuhyo, 14:109, 1952. Hora, J.: Nebennieren markaplasie und eigenartige Hautpigmentanomalie. Zentralbl. allg. Path. path. Anat., 81:52, 1943. Ito, M.: Studies on melanin: X. Incontinentia pigmenti. Tohoku J. exper. Med., 54:67, 1951. Jaramillo, R., Manterola, A., and Rosselot, J.: Incontinentia pigmenti. Rev. chil. Pediat., 19:654, 1948. Kawamura: Cited by Kitamura, 1954. Kitamura, K., Fukushiro, R., and Miyabayashi, T.: Incontinentia pigmenti in Tapan. Arch. Derm. & Syph., 69:667, 1954. Ktihling, F.: Incontinentia pigmenti. Dissertation, Wurzburg, 1949. Lapiere, S.: Incontinentia pigmenti. Arch, beiges. Derm. & Syph., 7:156, 1951. Levin, O.: Nevus reticularis and pigmentosus. Arch. Derm. & Syph., 27:141, 1933. Loveman, A. B., Fliegelman, M. T., Weidman, A. I., and Rein, C. R.: Incontinentia pigmenti: A re­ port of three additional cases. J. Pediat., 40:442, 1952. Miller, O. B., Arbesman, C, and Baer, R.: Disceminated herpes simplex (Kaposi's varicelliform erup­ tion). Arch. Derm. & Syph., 62:477,1950. Moncorps, C.: Incontinentia pigmenti bei einem 2l/i jahrigen Knaben. Ztschr. Haut u. Ges., 50:381, 1935. Murrell, T., and Lingamfelter, C.: Personal communication. Naegeli, O.: Familiarer Chromatophorennavus. Schweiz. med. Wschr., 97 :48, 1947. Philpott, J. A., Jr., Woodburne, A. R., and Philpott, O. S.: Incontinentia pigmenti. Arch. Derm. & Syph., 71:214, 1955. Pierini, L. E., Garcia, L. A., Pomposiello, I., and Rey, O.: Incontinentia pigmenti (Bloch-Sulzberger). Rev. argent. Dermatosif., 29:181, 1945. Rein, C. R., and Weidman, A. I.: Incontinentia pigmenti (Bloch-Sulzberger). Arch. Derm. & Syph., 65 :361, 1952. Scott, J. Graham, Friedmann, A. I., Chitters, M., and Pepler, W. J.: Ocular changes in the BlochSulzberger syndrome (incontinencia pigmenti). Brit. J. Ophth., 39 :276, 1955. Seidlmayer, K.: Ueber eine neues Syndrom multipler Abartung: Pigmentanomalie, Kongenitale ektodermale Nysplasia, hebenneirenmarkaplasie Ztsch. Kinderh., 63:451, 1942. Siemens, H. W.: Die Melanosis Corii Degenerativa, eine neue Pigmentdermatose. Arch. Derm. & Syph. (Berlin), 157:382, 1929. Sobel, N.: Incontinentia pigmenti. Arch. Derm. & Syph., 58:467, 1948. Sulzberger, M. B.: Ueber eine bisher nicht beschriebene congenitale Pigmentanomalie (incontinentia pigmenti). Arch. Derm. & Syph. (Berlin), 154:19, 1928. Sulzberger, M. B., and Bloom, D.: Incontinentia pigmenti. Arch. Derm. & Syph., 58:468, 1948. Sulzberger, M. B., Frazer, J. F., and Hunter, L.: Incontinentia pigmenti. Arch. Derm. & Syph., 38 :57, 1938. Uebel, H., Ludwig, A., and Korting, G.: Zur Kenntnis der Incontinentia Pigmenti (Bloch-Sulzberger). Arch. Derm. & Syph. (Berlin), 190:114, 1950. Watanabe: Cited by Kitamura, 1954.