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Urticaria pigmentosa
URTICARIA PIGMENTOSA REPORT OF A CASE OF THE BULLOUS VARIETY IN A NEWBORN INFANT A R T H U R LIPSCHUTZ,
M.D.,*
AND BERTRAM SHAFFER, M . D *~
PHILADELPHIA, PA.
RTICARIA pigmentosa in the newborn infant is an unusual U disorder. Even though in a busy children's hospital one may see several cases of this disease annually, the pediatric literature contains no report of this entity since 1929. We felt justified in reporting our case of urticaria pigmentosa, first, because the disease was actively present at the time of birth, second, because it was manifested as an acute bullous eruption, and finally, to point out the features of this rare disease to pediatricians. CASE REPORT
A. M. S., a white male infant, was born at term on Dec. 31, 1950, of a 33-year-old mother. The baby was the third sibling. A sister aged 7 years and a-brother aged 4 years are living and well. The mother's pregnancy was uneventful except for considerable emotional upset, evidenced particularly by sleeplessness and crying periods, during the first and second trimesters. Labor lasted approximately six hours with no complications. Immediately after birth a generalized skin eruption was noted covering the entire body but exempting the hands and feet. These lesions were described by the attending physician as ovM-shaped, smooth, brawny red, and maculopapular in character ranging in diameter from three-eighths to one inch. A few were surmounted by bullae . containing serous material. The infant's birth weight was 3,820 grams. His respirations and color *Department of Pediatrics, Sewish Hospital, Service of Dr. Aaron Capper. **Department of Dermatology, Mr. Sinai Hospital.
were normal, and except for his skin disorder, he presented no remarkable findings. The blood count showed 15 Gm. hemoglobin, 4,330,000 red blood cells, 12,543 white blood cells, with a normal differential count. A bacteriologic culture obtained from a bullous lesion revealed Aerobacter aerogenes. Because of the suspicion of intrauterine infection the baby was treated with 50,000 units of aqueous penicillin given intramuscularly every four hours for a period of fifteen days. No improvement followed and the infant was discharged Jan. 15, 1951. At this time he was seen by one of us (A. L.). His weight was 3,882 grams; he was taking an evaporated milk formula and, aside from his skin, was a well baby. The cutaneous examination on J a nua ry 17 by one of us (B. S.) revealed a widespread eruption involving most of the skin with the exception of the palms and soles. The trunk was most heavily involved. The individual lesions were blotchy but discrete, measuring from 1 to 3 cm. in diameter and varying in color from bright red to a dusky brown. The majority were oval or bipolar in shape. Most of the lesions were nodular but a few were of the macular type. At some sites frank wheals were found while other lesions seemed to describe transitional forms between the primary macular and nodular types and the secondary urtication. Many of the latter were of a distinct bullous character. There were no mucosal lesions. Stroking of the simple macular and nodular lesions and of the adjacent skin gave rise to definite urtication which, however, was limited t o the lesion sites only.
745
746
THE
J O U R N A L OF P E D I A T R I C S
F i g . 1 . - - P h o t o g r a p h to i l l u s t r a t e d i s t r i b u t i o n a n d g e n e r a l c h a r a c t e r o f t h e e r u p t i o n . T h e w i d e s l 0 r e a d d i s t r i b u t i o n , t h e b l o t c h y , i r r e g u l a r c h a r a c t e r o f t h e i n d i v i d u a l lesions, b u t w i t h a t e n d e n c y t o w a r d o v a l o r b i p o l a r outline, c a n be d i s t i n g u i s h e d .
F i g . 2 . - - A c l o s e - u p to i l l u s t r a t e t h e m a c u l a r a n d n o d u l a r c h a r a c t e r i s t i c s o f t h e lesions. S e v e r a l lesions in t h e c e n t e r of t h e b a c k a r e of a b u l l o u s t y p e . M a n y of t h e lesions s h o w whealing.
LIPSCHUTZ
AND SHAFFER:
The diagnosis 02 urticaria pigmentosa was made on the basis of the objective clinical findings described and the characteristic whealing of the lesions on stroking. Confirmation was obtained by a histologic study of one of the nodular lesions on the back taken on February 21.
Histologic Report (Dr. Herman Beerman).--The hematoxylin- and cosin-stained section showed marked hyperkeratosis of the epidermis with a moderate degree of acanthosis. The basal cell layer was intact. Hugging
URTICARIA PIGMENTOSA
747
not changed appreciably in color or number. The hemogram was normal and the infant was taking a cow's milk formula, a multiple vitamin preparation and cereal, and maintaining steady progress in growth and development. The baby seemed irritable at times because of the whealing which resulted from friction with his clothes. Ten m~lligrams of Benadryl Elixir were given three times daily for symptomatic relief but it did not reduce urtication, nor did it seem to make the child more comfortable.
Fig. 3.--Photomicrograph o f b i o p s y s e c t i o n ~ t a i n e d w i t h G i e m s a s t a i n to d e m o n s t r a t e t h e p r e s e n c e o f g r a n u l e s in t h e m a s t cells. I n t h i s i l l u s + r a t i o n t h e m a s t cells lie f r e e a s s p i n d l e - s h a p e d b o d i e s in t h e c o r i u m p a r a l l e l a n d c l o s e to t h e d e r m a l e p i d e r m a l j u n c t i o n .
tightly against the epidermis was an infiltrate having cuboidal and spindleshaped nuclei. This infiltrate was largely perivascular, but focal areas of infiltrate in the mid-corium were also observed. No dermal appendages were visualized. On Giemsa stain the infiltrate was found to be composed of mast cells. At 3 months of age, when the baby was last examined, his development was unretarded. His weight was 7,284 grams and he was 55 cm. in length. The lesions of the skin had
DISCUSSION
About 400 cases of urticaria pigmentosa have been reported since Nettleship described this condition in 1869.1, 2, 3,, Erlich 5 in ]879 first showed the diagnostic importance of mast cells as a positive pathognomonic feature of this disease when found in excessive amounts at the lesion sites. In addition, he demonstrated the increased pigment in the epidermis. The mast cell is a histiocyte, the cytoplasm of which contains meta-
748
T H E J O U R N A L OF PEDIATRICS
chromatic granules demonstrable as a purplish red color with toluene blue stains and red color with polychrome methylene blue stains. There is a great deal of evidence to support the contention that this material is heparin. When lying free in the tissues the mast cells are generally spindle shaped, but when compressed into closely packed aggregations they are likely to be cuboidal or oval in outline. In either case an oval or round nucleus is found. With hematoxylin and eosin staining the granules are not visible and the cytoplasm has a vacuolated appearance. Normally, mast cells appear in small numbers in all connective tissue, particularly in association with blood vessels2 Urticaria pigmentosa (synonym xanthelasmoidea)7, s, 9 usually begins in the third or fourth month of life. Less commonly it may have its onset at puberty or even in adult llfe. The disease is likely to be most active when it begins in infancy. At this time the lesions are red, urticarial, angry in appearance, and generally lacking in pigment. They may be mac ular, nodular, or hypertrophic. While usually discrete, in certain instances confluency develops and large tracts of skin may be involved as reddish, brownish, smooth or pigskinned formations. It is at this stage that the r a r e bullous lesions are most likely to be present. The extreme irritability of the lesions toward urtication and their occasional bullous development can be readily and characteristically elicited by stroking the lesions and the adjacent surrounding skin with the resultant formation of wheals ( a n d / o r bullae) at the lesion sites only (Darier's sign). The tendency toward spontaneous urtication gradually diminishes with periods of exacerbations and remissions over a period of ye,qrs although Darier's sign can usually be demonstrated. The lesions slowly change in color. In the beginning they are ]ikelv to be red but gradually take on a chamois, yellowish, brownish, red brown, or even slate brown color. They are also
likely to become flatter and more macular in type. While new lesions may appear in crops from time to time, the general tendency is for the process to become static and for the lesions to disappear in many instances completely at puberty. At other times, however, it may persist indefinitely. When urticaria pigmentosa has its onset in the adult, the macular-pigmented type is prone to dominate the clinical picture from the very beginning. The eruption may be situated anywhere on the skin but its site of predilection is the t runk where the lesions are usually most densely developed. Occasionally, brownish elevated spots have been described on the mucosa of the mouth as being part of this .eruption. Although the lesions are usually numerous and symmetrically disposed, in a few instances only isolated or few lesions have been described. Although itching is often present, especially w i t h the appearance of wheals, this is usually mild and not as a rule troublesome. Histologic examination of one of the lesions usually establishes the diagnosis. The characteristic finding is the presence of an increased number of mast cells. These cells are usually found in the papillae or high in the corium, but at times when large numbers are present, they may be apparent throughout the full thickness of the corium. They are most likely to be disDoscd about the blood vessels and the glandular structures of the skin. At times they appear t o lie between the collagenous fibers. When few in number they are scattered as spindle-shaped bodies, but when large numbers are present they accumulate as solid compact aggregations consisting of euboidal or round units. The earlier the lesion and the younger the patient, the more mast cells are likely to be found. Ill eruptions of many years' duration only normal numbers of mast cells may be present. Edema and lymphocytic infiltration may be seen but this usually depends
LIPSCHUTZ AND SHAFFER:
on the degree of w h e a l i n g p r e s e n t at the time of excision of the lesion. Except for increased pigment, which is a more o u t s t a n d i n g characteristic of the l a t e r lesions, no t y p i c a l change is present in the epidermis. Acanthosis, scaling, and edema m a y be f o u n d in v a r y i n g degrees. The cause of u r t i c a r i a p i g m e n t o s a is u n k n o w n . A congenital disorder with an o v e r p r o d u c t i o n of m a s t cells, p r e g n a n c y ]ate in life, vaccination, sulfur baths, fright, chicken pox, measles, and m a t e r n a l u p s e t d u r i n g p r e g n a n c y have been v a r i o u s l y assigned causes. 1~ 11 A k n o w l e d g e of the prognosis is of some i m p o r t a n c e in as m u c h as the eruption in m a n y of these children disappears s p o n t a n e o u s l y b y p u b e r t y . This will t e n d to alleviate the stress under which p a r e n t s live f o r years. U n f o r t u n a t e l y to date there is no curative t r e a t m e n t . Soothing antipruritic ointments and antihistamine so'ntions offer some p r o t e c t i o n for restless patients, s Sometimes x - r a y thera p y clears u p the lesions b u t does not p r e v e n t recurrence. Since the symptoms in most cases usually decrease f r o m y e a r to y e a r and the disease tends to heal in a d v a n c e d life, it is best to adhere to c o n s e r v a t i v e measures only. Recently, Ellis 4 r e p o r t e d a case of u r t i c a r i a p i g m e n t o s a in a N e g r o female i n f a n t who died at 12 months of age. He was able to d e m o n s t r a t e the presence of m a s t cells in increased a m o u n t s in various organs of the b o d y as well as the skin and conseq u e n t l y concluded t h a t the disease is a systemic r a t h e r t h a n a local cutaneous manifestation. SUMMARY
1. A case of u r t i c a r i a p i g m e n t o s a in an i n f a n t is reported.
URTICARIA PIGMENTOSA
749
2. The special f e a t u r e s of interest in this case are the presence of the full-blown disease picture at birth a n d the bullous c h a r a c t e r of m a n y of the lesions. 3. Attention is called to the absence of cases r e p o r t e d in the recent pediatric literature. F o r t h a t reason the disease picture a n d its p a t h o g n o m o n i c clinical sign (urtication on s t r o k i n g of the lesion) are described. 4. The presence of m a s t cells in abn o r m a l n u m b e r s in the corium on histologic e x a m i n a t i o n is pointed out as a characteristic pathologic feature. REFERENCES I. Nettleship: Chronic Urticaria Leaving Brown Stains: Nearly Two Years' Dulation, Brit. IYI. J. 2: 323, 1869. 2. Little, G.: A Contribution to the Study of Urticaria Pigmentosa, Brit. J. Dermat. & Syph. 17: 355, 393, 427, 1905; 18: 16, 1906. 3. Finnerud, C. W.: Urticaria Pigmentosa (Nodular Type) With a Summary of the Literature, Arch. Dermat. & Syph. 8: 344, 1923. 4. Ellis, J. 3/L: Urticaria Pigmentosa: A Report of a Case W i t h Autopsy, Arch. P a t h . 48: 426, 1949. 5. Erlieh, P.: Arch. Anat. u. Physiol. 3: ]66, 1879; 4: 57], 1879. 6. Lever, W. F.: Histopathology of the Skin, Philadelphia, 1949, J. B. Lippincott Co., p. 33. 7. Ormsby, O. S., and Montgomery, H.: Diseases of the Skin, Philadelphia, 1948, Lea & Febiger, pp. 177-181. 8. Ahlswede, E.: Urticaria Pigmentosa: P r a c t i c a l T r e a t m e n t of Skin Diseases, New York, 1932, Paul B. Hoeber, pp. 654-655. 9. McQuarrie, I.: B r e n n e m a n n ' s P r a c t i c e of Pediatrics, vol. IV, Hagerstown, 3/Id., 1948, W. F. P r i o r Co., pp. 45-46. 10. Ray, It., and Kiyasu, K.: Urticaria P i g m e n t o s a in Children: Report of a Nodular Case and Review of the Literature, Am. J. Dis. Child. 38: 1040, 1929. 11. Mount, L. B.: U r t i c a r i a Pigmentosa, Arch. Dermat. & Syph. 14: 715, 1926.
M.D.,*
AND BERTRAM SHAFFER, M . D *~
PHILADELPHIA, PA.
RTICARIA pigmentosa in the newborn infant is an unusual U disorder. Even though in a busy children's hospital one may see several cases of this disease annually, the pediatric literature contains no report of this entity since 1929. We felt justified in reporting our case of urticaria pigmentosa, first, because the disease was actively present at the time of birth, second, because it was manifested as an acute bullous eruption, and finally, to point out the features of this rare disease to pediatricians. CASE REPORT
A. M. S., a white male infant, was born at term on Dec. 31, 1950, of a 33-year-old mother. The baby was the third sibling. A sister aged 7 years and a-brother aged 4 years are living and well. The mother's pregnancy was uneventful except for considerable emotional upset, evidenced particularly by sleeplessness and crying periods, during the first and second trimesters. Labor lasted approximately six hours with no complications. Immediately after birth a generalized skin eruption was noted covering the entire body but exempting the hands and feet. These lesions were described by the attending physician as ovM-shaped, smooth, brawny red, and maculopapular in character ranging in diameter from three-eighths to one inch. A few were surmounted by bullae . containing serous material. The infant's birth weight was 3,820 grams. His respirations and color *Department of Pediatrics, Sewish Hospital, Service of Dr. Aaron Capper. **Department of Dermatology, Mr. Sinai Hospital.
were normal, and except for his skin disorder, he presented no remarkable findings. The blood count showed 15 Gm. hemoglobin, 4,330,000 red blood cells, 12,543 white blood cells, with a normal differential count. A bacteriologic culture obtained from a bullous lesion revealed Aerobacter aerogenes. Because of the suspicion of intrauterine infection the baby was treated with 50,000 units of aqueous penicillin given intramuscularly every four hours for a period of fifteen days. No improvement followed and the infant was discharged Jan. 15, 1951. At this time he was seen by one of us (A. L.). His weight was 3,882 grams; he was taking an evaporated milk formula and, aside from his skin, was a well baby. The cutaneous examination on J a nua ry 17 by one of us (B. S.) revealed a widespread eruption involving most of the skin with the exception of the palms and soles. The trunk was most heavily involved. The individual lesions were blotchy but discrete, measuring from 1 to 3 cm. in diameter and varying in color from bright red to a dusky brown. The majority were oval or bipolar in shape. Most of the lesions were nodular but a few were of the macular type. At some sites frank wheals were found while other lesions seemed to describe transitional forms between the primary macular and nodular types and the secondary urtication. Many of the latter were of a distinct bullous character. There were no mucosal lesions. Stroking of the simple macular and nodular lesions and of the adjacent skin gave rise to definite urtication which, however, was limited t o the lesion sites only.
745
746
THE
J O U R N A L OF P E D I A T R I C S
F i g . 1 . - - P h o t o g r a p h to i l l u s t r a t e d i s t r i b u t i o n a n d g e n e r a l c h a r a c t e r o f t h e e r u p t i o n . T h e w i d e s l 0 r e a d d i s t r i b u t i o n , t h e b l o t c h y , i r r e g u l a r c h a r a c t e r o f t h e i n d i v i d u a l lesions, b u t w i t h a t e n d e n c y t o w a r d o v a l o r b i p o l a r outline, c a n be d i s t i n g u i s h e d .
F i g . 2 . - - A c l o s e - u p to i l l u s t r a t e t h e m a c u l a r a n d n o d u l a r c h a r a c t e r i s t i c s o f t h e lesions. S e v e r a l lesions in t h e c e n t e r of t h e b a c k a r e of a b u l l o u s t y p e . M a n y of t h e lesions s h o w whealing.
LIPSCHUTZ
AND SHAFFER:
The diagnosis 02 urticaria pigmentosa was made on the basis of the objective clinical findings described and the characteristic whealing of the lesions on stroking. Confirmation was obtained by a histologic study of one of the nodular lesions on the back taken on February 21.
Histologic Report (Dr. Herman Beerman).--The hematoxylin- and cosin-stained section showed marked hyperkeratosis of the epidermis with a moderate degree of acanthosis. The basal cell layer was intact. Hugging
URTICARIA PIGMENTOSA
747
not changed appreciably in color or number. The hemogram was normal and the infant was taking a cow's milk formula, a multiple vitamin preparation and cereal, and maintaining steady progress in growth and development. The baby seemed irritable at times because of the whealing which resulted from friction with his clothes. Ten m~lligrams of Benadryl Elixir were given three times daily for symptomatic relief but it did not reduce urtication, nor did it seem to make the child more comfortable.
Fig. 3.--Photomicrograph o f b i o p s y s e c t i o n ~ t a i n e d w i t h G i e m s a s t a i n to d e m o n s t r a t e t h e p r e s e n c e o f g r a n u l e s in t h e m a s t cells. I n t h i s i l l u s + r a t i o n t h e m a s t cells lie f r e e a s s p i n d l e - s h a p e d b o d i e s in t h e c o r i u m p a r a l l e l a n d c l o s e to t h e d e r m a l e p i d e r m a l j u n c t i o n .
tightly against the epidermis was an infiltrate having cuboidal and spindleshaped nuclei. This infiltrate was largely perivascular, but focal areas of infiltrate in the mid-corium were also observed. No dermal appendages were visualized. On Giemsa stain the infiltrate was found to be composed of mast cells. At 3 months of age, when the baby was last examined, his development was unretarded. His weight was 7,284 grams and he was 55 cm. in length. The lesions of the skin had
DISCUSSION
About 400 cases of urticaria pigmentosa have been reported since Nettleship described this condition in 1869.1, 2, 3,, Erlich 5 in ]879 first showed the diagnostic importance of mast cells as a positive pathognomonic feature of this disease when found in excessive amounts at the lesion sites. In addition, he demonstrated the increased pigment in the epidermis. The mast cell is a histiocyte, the cytoplasm of which contains meta-
748
T H E J O U R N A L OF PEDIATRICS
chromatic granules demonstrable as a purplish red color with toluene blue stains and red color with polychrome methylene blue stains. There is a great deal of evidence to support the contention that this material is heparin. When lying free in the tissues the mast cells are generally spindle shaped, but when compressed into closely packed aggregations they are likely to be cuboidal or oval in outline. In either case an oval or round nucleus is found. With hematoxylin and eosin staining the granules are not visible and the cytoplasm has a vacuolated appearance. Normally, mast cells appear in small numbers in all connective tissue, particularly in association with blood vessels2 Urticaria pigmentosa (synonym xanthelasmoidea)7, s, 9 usually begins in the third or fourth month of life. Less commonly it may have its onset at puberty or even in adult llfe. The disease is likely to be most active when it begins in infancy. At this time the lesions are red, urticarial, angry in appearance, and generally lacking in pigment. They may be mac ular, nodular, or hypertrophic. While usually discrete, in certain instances confluency develops and large tracts of skin may be involved as reddish, brownish, smooth or pigskinned formations. It is at this stage that the r a r e bullous lesions are most likely to be present. The extreme irritability of the lesions toward urtication and their occasional bullous development can be readily and characteristically elicited by stroking the lesions and the adjacent surrounding skin with the resultant formation of wheals ( a n d / o r bullae) at the lesion sites only (Darier's sign). The tendency toward spontaneous urtication gradually diminishes with periods of exacerbations and remissions over a period of ye,qrs although Darier's sign can usually be demonstrated. The lesions slowly change in color. In the beginning they are ]ikelv to be red but gradually take on a chamois, yellowish, brownish, red brown, or even slate brown color. They are also
likely to become flatter and more macular in type. While new lesions may appear in crops from time to time, the general tendency is for the process to become static and for the lesions to disappear in many instances completely at puberty. At other times, however, it may persist indefinitely. When urticaria pigmentosa has its onset in the adult, the macular-pigmented type is prone to dominate the clinical picture from the very beginning. The eruption may be situated anywhere on the skin but its site of predilection is the t runk where the lesions are usually most densely developed. Occasionally, brownish elevated spots have been described on the mucosa of the mouth as being part of this .eruption. Although the lesions are usually numerous and symmetrically disposed, in a few instances only isolated or few lesions have been described. Although itching is often present, especially w i t h the appearance of wheals, this is usually mild and not as a rule troublesome. Histologic examination of one of the lesions usually establishes the diagnosis. The characteristic finding is the presence of an increased number of mast cells. These cells are usually found in the papillae or high in the corium, but at times when large numbers are present, they may be apparent throughout the full thickness of the corium. They are most likely to be disDoscd about the blood vessels and the glandular structures of the skin. At times they appear t o lie between the collagenous fibers. When few in number they are scattered as spindle-shaped bodies, but when large numbers are present they accumulate as solid compact aggregations consisting of euboidal or round units. The earlier the lesion and the younger the patient, the more mast cells are likely to be found. Ill eruptions of many years' duration only normal numbers of mast cells may be present. Edema and lymphocytic infiltration may be seen but this usually depends
LIPSCHUTZ AND SHAFFER:
on the degree of w h e a l i n g p r e s e n t at the time of excision of the lesion. Except for increased pigment, which is a more o u t s t a n d i n g characteristic of the l a t e r lesions, no t y p i c a l change is present in the epidermis. Acanthosis, scaling, and edema m a y be f o u n d in v a r y i n g degrees. The cause of u r t i c a r i a p i g m e n t o s a is u n k n o w n . A congenital disorder with an o v e r p r o d u c t i o n of m a s t cells, p r e g n a n c y ]ate in life, vaccination, sulfur baths, fright, chicken pox, measles, and m a t e r n a l u p s e t d u r i n g p r e g n a n c y have been v a r i o u s l y assigned causes. 1~ 11 A k n o w l e d g e of the prognosis is of some i m p o r t a n c e in as m u c h as the eruption in m a n y of these children disappears s p o n t a n e o u s l y b y p u b e r t y . This will t e n d to alleviate the stress under which p a r e n t s live f o r years. U n f o r t u n a t e l y to date there is no curative t r e a t m e n t . Soothing antipruritic ointments and antihistamine so'ntions offer some p r o t e c t i o n for restless patients, s Sometimes x - r a y thera p y clears u p the lesions b u t does not p r e v e n t recurrence. Since the symptoms in most cases usually decrease f r o m y e a r to y e a r and the disease tends to heal in a d v a n c e d life, it is best to adhere to c o n s e r v a t i v e measures only. Recently, Ellis 4 r e p o r t e d a case of u r t i c a r i a p i g m e n t o s a in a N e g r o female i n f a n t who died at 12 months of age. He was able to d e m o n s t r a t e the presence of m a s t cells in increased a m o u n t s in various organs of the b o d y as well as the skin and conseq u e n t l y concluded t h a t the disease is a systemic r a t h e r t h a n a local cutaneous manifestation. SUMMARY
1. A case of u r t i c a r i a p i g m e n t o s a in an i n f a n t is reported.
URTICARIA PIGMENTOSA
749
2. The special f e a t u r e s of interest in this case are the presence of the full-blown disease picture at birth a n d the bullous c h a r a c t e r of m a n y of the lesions. 3. Attention is called to the absence of cases r e p o r t e d in the recent pediatric literature. F o r t h a t reason the disease picture a n d its p a t h o g n o m o n i c clinical sign (urtication on s t r o k i n g of the lesion) are described. 4. The presence of m a s t cells in abn o r m a l n u m b e r s in the corium on histologic e x a m i n a t i o n is pointed out as a characteristic pathologic feature. REFERENCES I. Nettleship: Chronic Urticaria Leaving Brown Stains: Nearly Two Years' Dulation, Brit. IYI. J. 2: 323, 1869. 2. Little, G.: A Contribution to the Study of Urticaria Pigmentosa, Brit. J. Dermat. & Syph. 17: 355, 393, 427, 1905; 18: 16, 1906. 3. Finnerud, C. W.: Urticaria Pigmentosa (Nodular Type) With a Summary of the Literature, Arch. Dermat. & Syph. 8: 344, 1923. 4. Ellis, J. 3/L: Urticaria Pigmentosa: A Report of a Case W i t h Autopsy, Arch. P a t h . 48: 426, 1949. 5. Erlieh, P.: Arch. Anat. u. Physiol. 3: ]66, 1879; 4: 57], 1879. 6. Lever, W. F.: Histopathology of the Skin, Philadelphia, 1949, J. B. Lippincott Co., p. 33. 7. Ormsby, O. S., and Montgomery, H.: Diseases of the Skin, Philadelphia, 1948, Lea & Febiger, pp. 177-181. 8. Ahlswede, E.: Urticaria Pigmentosa: P r a c t i c a l T r e a t m e n t of Skin Diseases, New York, 1932, Paul B. Hoeber, pp. 654-655. 9. McQuarrie, I.: B r e n n e m a n n ' s P r a c t i c e of Pediatrics, vol. IV, Hagerstown, 3/Id., 1948, W. F. P r i o r Co., pp. 45-46. 10. Ray, It., and Kiyasu, K.: Urticaria P i g m e n t o s a in Children: Report of a Nodular Case and Review of the Literature, Am. J. Dis. Child. 38: 1040, 1929. 11. Mount, L. B.: U r t i c a r i a Pigmentosa, Arch. Dermat. & Syph. 14: 715, 1926.