International Journal of Pediatric Otorhinolaryngology, @ Elsevier/North-Holland Biomedical Press
WOAKES’ SYNDROME: POLYPS
B. KELLERHALS University
THE PROBLEMS
1 (1979)
79-85
OF INFANTILE
79
NASAL
and B. de UTHEMANN
ENT department,
Znselspital,
CH-3010 Bern (Switzerland)
(Originally presented at the First World Congress of Pediatric Otorhinolaryngology, in Sirmione, Italy on April 26-30th, 1977)
SUMMARY
Usually, nasal polyposis in early childhood (children aged less than 5 years) is caused by cystic fibrosis or Kartagener’s syndrome. In later age groups, recurrent sinus infections, allergy and ASA disease (asthma, aspirin intolerance and nasal polyps) have to be taken into consideration. Four cases of early childhood polyposis are reported which fit into none of these etiological groups. This newly defined Woakes’ syndrome comprises recurrent nasal polyposis with broadening of the nose, frontal sinus aplasia, bronchiectasis, and dyscrinia (production of highly viscous mucus). The disease seems to be hereditary. The possible origins of the disease are discussed.
INTRODUCTION
In the proceedings of the London Medical Society [ 131 it is reported that in 1885 a Dr. Woakes “read a lengthy paper” on necrosing ethmoiditis and nasal polyps with broadening of the nose. That was the birth of Woakes’ syndrome - a term whose history has followed an equally lengthy and rather serpentine course during the following decades. Many authors [1,2,5,6,10] have tried to find out what kind of polyps Woakes had seen. Eventually, various types of nasal polyps have been termed Woakes’ disease, sometimes with rather poor attempts to give a precise definition with clear criteria for differential diagnosis. The present study reports 4 cases of severe recurrent infantile nasal polyposis with broadening of the nose. To date no similar cases have been reported in the literature. Our cases therefore require the definition of a new syndrome which might be called by the name of Woakes.
80 TABLE I
blocking
of nasal airways
nasal polyps and nose broadening since age of
since birth
since birth
6 yrs.
6 yrs.
number of polypectomies
6
2
dyscrinia
+
+
frontal sinus aplasia
+
+
bronchiectasis
-t?
+
allergy
negative
negative
sweat tests
negative
negative
CASE REPORTS
Two pairs of children of unrelated families (Tables I and II) developed nasal obstruction, almost since birth. The families are not tainted with hereditary diseases; especially no cases of asthma or allergy were found. In all children the nose started to widen at the age of 2-3 years (Fig. 1). Even-
TABLE II
nasal polyps and nose broadening since number
of polypectomies
dyscrinia frontal
sinus aplasia
bronchiectasis allergy sweat
tests
age of
2-3
years 15
2-3 years 5
+
+
+
+
+
+
negative
negative
negative
negative
81
Fig. 1. Nose deformities.
Fig. 2. Histopathology
Left: Patient A.K. (11 years). Right: patient SK. (9 years).
of the nasal polyps in Woakes’ syndrome.
82
tually the existence of severe nasal polyposis was established by rhinoscopy. Polypectomies were repeatedly performed. All children complained about abundant nasal discharge, the secretions being of a rubber-like viscosity. Further examination revealed frontal sinus aplasia, bronchiectasis with clubbed fingers, but no visceral transposition. Intensive testing (scratch tests, serum electrophoresis and immunoelectrophoresis, serum IgE and excretory IgA measurements) showed no signs of allergic disease. AlI children were repeatedly tested for cystic fibrosis, but sweat tests were definitely normal, and none ever complained about digestive troubles. Histopathologically, the polyps presented the usual features of inflammatory polyposis (Fig. 2). The epithelial layer and the mucous glands appeared normal, and the number of IgA-producing plasma cells was considered to be within normal limits. DISCUSSION
Nasal polyps in early childhood are an extremely rare condition. An American study [8] gave the incidence of nasal polyps in adults as being 0.2%, whereas in children the incidence was 10 times lower. In children of less than 5 years, cystic fibrosis is the predominant etiology of nasal polyposis. Shwachman et al. [ 111 found 6.7% of cystic fibrosis patients to have nasal polyps, and Caplin et al. [7] reported a percentage of ll-27%. Kartagener’s syndrome is another rare hereditary syndrome which can cause early formation of nasal polyps. Usually, the atopic child does not produce nasal polyps before the age of 5 years, and in all age groups less than 1% of atopic children develop nasal polyposis [7]. In children of more than 5 years, the incidence of nasal polyposis starts to rise, and recurrent sinus infections become the predominant etiology. Aspirin intolerance, too, leads to polyp formation in later age groups only. Our 4 cases developed nasal polyposis already in early childhood. Their case histories as well as their clinical and laboratory findings fit neither the diagnosis of cystic fibrosis nor that of Kartagener’s syndrome. The differential diagnosis of those syndromes is shown in Table III. An atopic disease was excluded by extensive testing, and the ASA disease (asthma, aspirin intolerance and nasal polyps) was excluded, too, by the absence of asthma, the lack of aspirin intolerance cases in the family history, and by the early onset of polyposis. An extensive literature review [ 121 revealed not a single similar case, if we exclude all cases not properly tested for allergy or cystic fibrosis. Therefore, our cases seem to belong to a new nosological entity, which requires a new definition. In honour of the original description of Dr. Woakes, we will term this entity Woakes’syndrome. Our new definition comprises severe recurrent nasal polyps in early childhood with broadening of the nose, nasal dyscrinia (= production of abnormally viscous nasal secretions), frontal sinus aplasia and bronchiectasis. The disease seems to be hereditary.
83 TABLE III DIFFERENTIAL DIAGNOSIS AND WOAKES’ SYNDROME
nasal
OF CYSTIC FIBROSIS, KARTAGENER’S
cystic
Kartagener’s
Woake’s
fibrosis
syndrome
syndrome
polyps
(+I
(+I
+
+
+
+
frontal sinus aplasia
-
+
+
situs
-
+
+
+
+
(+I
(+I
+
+
+
+
bronchiectasis
inversus
dyscrinia
SYNDROME
allergy sweat tests nose
broadening
heredity
+
The precise nature of the genetic defect remains unknown. If we assume an inborn defect of the mucus production, all other symptoms could be derived from the highly increased mucus viscosity. Abnormally viscous secretions in the upper and lower airways might be responsible for recurrent sinus infections with frontal sinus aplasia and polyp formation due to stagnant mucus that blocks the sinus orifices. Mechanically, the nasal polyps progressively extend the growing nasal skeleton. In the lower airways, the evolution might lead to bronchiectasis. The children’s nasal secretions show an increased amount of acid glycoprotein fibrils (Fig. 3) as can be seen in polarized light microscopy after toluidine blue staining and washing with alcoholic aniline solution. In bronchial secretions these glycoprotein fibrils are known to reflect an enhanced viscosity [ 3,4]. The prognosis seems to be less obscured by the upper airway symptoms than by the degree of bronchial alterations. After puberty, the eldest of our cases showed a spontaneous regression of the polyp formation. The remaining 3 cases will show whether such a favorable evolution can be expected in future cases of Woakes’ syndrome. The hypothesis that abnormally viscous secretions are the original defect, led to the assumption that a long-term treatment with acetylcysteine (Fluimucil) might delay the recurrence of polyps. In vitro tests (Fig. 4) show that acetylcysteine dissolves the patient’s nasal secretions much easier than bromhexine (Bisolvon) or S-carboxymethylcysteine (Rhinathiol). After 1 year of continuous peroral administration of acetylcysteine, the children presented a
84
Fig. 3. Left: acid glycoprotein
fibrils in the nasal secretions.
Fig. 4. Right: in vitro dissolution of nasal secretions: bromhexine (left), S-carboxymethylcysteine (center) and acetylcysteine (right).
slower pace of polyp formation, although the recurrence of polyps could not be prevented completely. In all cases corticosteroids had no significant effect. Any concomitant airway infection has to be treated with antibiotics. The surgical procedure has to include a careful ethmoidectomy. After puberty, the broadening of the nasal bridge can be corrected by rhinoplasty. REFERENCES 1 Appaix, A. and Robert, J., Polypose deformante et recidivante des jeunes (Maladie de Woakes), Rev. Laryng. (Bordeaux), 74 (1953) 216-254. 2 Bouche, J., Freche, Ch. and Chevalier, J., A propos d’un cas recent opCB de maladie de Woakes, Ann. Oto-laryng. (Paris), 83 (1966) 443-446. Biirgi, H., Fibre systems in sputum, Bull. Physio-Path. Resp., 9 (1973) 191. Biirgi, H., Rheologie des Sputums. In Toux-Tussis-Husten, Hommel, 1975. Busca, G.P., La sindrome di Woakes, Minerva Otorinolaring., 16 (1966) 201-205. Canyut, M. and Terracol, J., La polypose nasale recidivante et deformante des jeunes. Rev. Laryng. Otol. (Bordeaux), 45 (1924) 7. 7 Caplin, I. et al., Are nasal polyps an allergic phenomenon? Ann. Allergy, 29 (1971) 631. 8 Falliers, C.J., Familial coincidence of asthma, aspirin intolerance and nasal polyposis, Ann. Allergy, 32 (1974) 65. 9 Lanoff, G., Daddono, A. and Johnson, E., Nasal polyps in children, Ann. Allergy, 31 (1973) 551. 10 Mounier-Kuhn, P., Le syndrome ethmoido-antrite et bronchiectasies, Ann. Oto-laryng. (Paris), 12 (1945) 387.
85 11 Shwachman, H. et al., Nasal polyposis in patients with cystic fibrosis, Pediatrics, 30 (1962) 389. 12 de Uthemann, B., Zur Problematik der kindlichen Polyposis Nasi (Woakes-Syndrom), Thesis, Bern, 1976. 13 Woakes, E., Necrosing ethmoiditis and mucous polypi, Lancet, i (1885) 619.
WOAKES’ SYNDROME: POLYPS
B. KELLERHALS University
THE PROBLEMS
1 (1979)
79-85
OF INFANTILE
79
NASAL
and B. de UTHEMANN
ENT department,
Znselspital,
CH-3010 Bern (Switzerland)
(Originally presented at the First World Congress of Pediatric Otorhinolaryngology, in Sirmione, Italy on April 26-30th, 1977)
SUMMARY
Usually, nasal polyposis in early childhood (children aged less than 5 years) is caused by cystic fibrosis or Kartagener’s syndrome. In later age groups, recurrent sinus infections, allergy and ASA disease (asthma, aspirin intolerance and nasal polyps) have to be taken into consideration. Four cases of early childhood polyposis are reported which fit into none of these etiological groups. This newly defined Woakes’ syndrome comprises recurrent nasal polyposis with broadening of the nose, frontal sinus aplasia, bronchiectasis, and dyscrinia (production of highly viscous mucus). The disease seems to be hereditary. The possible origins of the disease are discussed.
INTRODUCTION
In the proceedings of the London Medical Society [ 131 it is reported that in 1885 a Dr. Woakes “read a lengthy paper” on necrosing ethmoiditis and nasal polyps with broadening of the nose. That was the birth of Woakes’ syndrome - a term whose history has followed an equally lengthy and rather serpentine course during the following decades. Many authors [1,2,5,6,10] have tried to find out what kind of polyps Woakes had seen. Eventually, various types of nasal polyps have been termed Woakes’ disease, sometimes with rather poor attempts to give a precise definition with clear criteria for differential diagnosis. The present study reports 4 cases of severe recurrent infantile nasal polyposis with broadening of the nose. To date no similar cases have been reported in the literature. Our cases therefore require the definition of a new syndrome which might be called by the name of Woakes.
80 TABLE I
blocking
of nasal airways
nasal polyps and nose broadening since age of
since birth
since birth
6 yrs.
6 yrs.
number of polypectomies
6
2
dyscrinia
+
+
frontal sinus aplasia
+
+
bronchiectasis
-t?
+
allergy
negative
negative
sweat tests
negative
negative
CASE REPORTS
Two pairs of children of unrelated families (Tables I and II) developed nasal obstruction, almost since birth. The families are not tainted with hereditary diseases; especially no cases of asthma or allergy were found. In all children the nose started to widen at the age of 2-3 years (Fig. 1). Even-
TABLE II
nasal polyps and nose broadening since number
of polypectomies
dyscrinia frontal
sinus aplasia
bronchiectasis allergy sweat
tests
age of
2-3
years 15
2-3 years 5
+
+
+
+
+
+
negative
negative
negative
negative
81
Fig. 1. Nose deformities.
Fig. 2. Histopathology
Left: Patient A.K. (11 years). Right: patient SK. (9 years).
of the nasal polyps in Woakes’ syndrome.
82
tually the existence of severe nasal polyposis was established by rhinoscopy. Polypectomies were repeatedly performed. All children complained about abundant nasal discharge, the secretions being of a rubber-like viscosity. Further examination revealed frontal sinus aplasia, bronchiectasis with clubbed fingers, but no visceral transposition. Intensive testing (scratch tests, serum electrophoresis and immunoelectrophoresis, serum IgE and excretory IgA measurements) showed no signs of allergic disease. AlI children were repeatedly tested for cystic fibrosis, but sweat tests were definitely normal, and none ever complained about digestive troubles. Histopathologically, the polyps presented the usual features of inflammatory polyposis (Fig. 2). The epithelial layer and the mucous glands appeared normal, and the number of IgA-producing plasma cells was considered to be within normal limits. DISCUSSION
Nasal polyps in early childhood are an extremely rare condition. An American study [8] gave the incidence of nasal polyps in adults as being 0.2%, whereas in children the incidence was 10 times lower. In children of less than 5 years, cystic fibrosis is the predominant etiology of nasal polyposis. Shwachman et al. [ 111 found 6.7% of cystic fibrosis patients to have nasal polyps, and Caplin et al. [7] reported a percentage of ll-27%. Kartagener’s syndrome is another rare hereditary syndrome which can cause early formation of nasal polyps. Usually, the atopic child does not produce nasal polyps before the age of 5 years, and in all age groups less than 1% of atopic children develop nasal polyposis [7]. In children of more than 5 years, the incidence of nasal polyposis starts to rise, and recurrent sinus infections become the predominant etiology. Aspirin intolerance, too, leads to polyp formation in later age groups only. Our 4 cases developed nasal polyposis already in early childhood. Their case histories as well as their clinical and laboratory findings fit neither the diagnosis of cystic fibrosis nor that of Kartagener’s syndrome. The differential diagnosis of those syndromes is shown in Table III. An atopic disease was excluded by extensive testing, and the ASA disease (asthma, aspirin intolerance and nasal polyps) was excluded, too, by the absence of asthma, the lack of aspirin intolerance cases in the family history, and by the early onset of polyposis. An extensive literature review [ 121 revealed not a single similar case, if we exclude all cases not properly tested for allergy or cystic fibrosis. Therefore, our cases seem to belong to a new nosological entity, which requires a new definition. In honour of the original description of Dr. Woakes, we will term this entity Woakes’syndrome. Our new definition comprises severe recurrent nasal polyps in early childhood with broadening of the nose, nasal dyscrinia (= production of abnormally viscous nasal secretions), frontal sinus aplasia and bronchiectasis. The disease seems to be hereditary.
83 TABLE III DIFFERENTIAL DIAGNOSIS AND WOAKES’ SYNDROME
nasal
OF CYSTIC FIBROSIS, KARTAGENER’S
cystic
Kartagener’s
Woake’s
fibrosis
syndrome
syndrome
polyps
(+I
(+I
+
+
+
+
frontal sinus aplasia
-
+
+
situs
-
+
+
+
+
(+I
(+I
+
+
+
+
bronchiectasis
inversus
dyscrinia
SYNDROME
allergy sweat tests nose
broadening
heredity
+
The precise nature of the genetic defect remains unknown. If we assume an inborn defect of the mucus production, all other symptoms could be derived from the highly increased mucus viscosity. Abnormally viscous secretions in the upper and lower airways might be responsible for recurrent sinus infections with frontal sinus aplasia and polyp formation due to stagnant mucus that blocks the sinus orifices. Mechanically, the nasal polyps progressively extend the growing nasal skeleton. In the lower airways, the evolution might lead to bronchiectasis. The children’s nasal secretions show an increased amount of acid glycoprotein fibrils (Fig. 3) as can be seen in polarized light microscopy after toluidine blue staining and washing with alcoholic aniline solution. In bronchial secretions these glycoprotein fibrils are known to reflect an enhanced viscosity [ 3,4]. The prognosis seems to be less obscured by the upper airway symptoms than by the degree of bronchial alterations. After puberty, the eldest of our cases showed a spontaneous regression of the polyp formation. The remaining 3 cases will show whether such a favorable evolution can be expected in future cases of Woakes’ syndrome. The hypothesis that abnormally viscous secretions are the original defect, led to the assumption that a long-term treatment with acetylcysteine (Fluimucil) might delay the recurrence of polyps. In vitro tests (Fig. 4) show that acetylcysteine dissolves the patient’s nasal secretions much easier than bromhexine (Bisolvon) or S-carboxymethylcysteine (Rhinathiol). After 1 year of continuous peroral administration of acetylcysteine, the children presented a
84
Fig. 3. Left: acid glycoprotein
fibrils in the nasal secretions.
Fig. 4. Right: in vitro dissolution of nasal secretions: bromhexine (left), S-carboxymethylcysteine (center) and acetylcysteine (right).
slower pace of polyp formation, although the recurrence of polyps could not be prevented completely. In all cases corticosteroids had no significant effect. Any concomitant airway infection has to be treated with antibiotics. The surgical procedure has to include a careful ethmoidectomy. After puberty, the broadening of the nasal bridge can be corrected by rhinoplasty. REFERENCES 1 Appaix, A. and Robert, J., Polypose deformante et recidivante des jeunes (Maladie de Woakes), Rev. Laryng. (Bordeaux), 74 (1953) 216-254. 2 Bouche, J., Freche, Ch. and Chevalier, J., A propos d’un cas recent opCB de maladie de Woakes, Ann. Oto-laryng. (Paris), 83 (1966) 443-446. Biirgi, H., Fibre systems in sputum, Bull. Physio-Path. Resp., 9 (1973) 191. Biirgi, H., Rheologie des Sputums. In Toux-Tussis-Husten, Hommel, 1975. Busca, G.P., La sindrome di Woakes, Minerva Otorinolaring., 16 (1966) 201-205. Canyut, M. and Terracol, J., La polypose nasale recidivante et deformante des jeunes. Rev. Laryng. Otol. (Bordeaux), 45 (1924) 7. 7 Caplin, I. et al., Are nasal polyps an allergic phenomenon? Ann. Allergy, 29 (1971) 631. 8 Falliers, C.J., Familial coincidence of asthma, aspirin intolerance and nasal polyposis, Ann. Allergy, 32 (1974) 65. 9 Lanoff, G., Daddono, A. and Johnson, E., Nasal polyps in children, Ann. Allergy, 31 (1973) 551. 10 Mounier-Kuhn, P., Le syndrome ethmoido-antrite et bronchiectasies, Ann. Oto-laryng. (Paris), 12 (1945) 387.
85 11 Shwachman, H. et al., Nasal polyposis in patients with cystic fibrosis, Pediatrics, 30 (1962) 389. 12 de Uthemann, B., Zur Problematik der kindlichen Polyposis Nasi (Woakes-Syndrom), Thesis, Bern, 1976. 13 Woakes, E., Necrosing ethmoiditis and mucous polypi, Lancet, i (1885) 619.
