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Woakes’ syndrome and albinism
Auris Nasus Larynx 34 (2007) 245–248 www.elsevier.com/locate/anl
Woakes’ syndrome and albinism Marco Caversaccio a,*, Ariane Baumann a, Arthur Helbling b a
b
Department of ENT, Head and Neck Surgery, University Hospital, Inselspital, 3010 Bern, Switzerland Department of Policlinics of Allergology and Clinical Immunology, Inselspital, University of Bern, Switzerland Received 4 July 2006; accepted 25 September 2006 Available online 19 December 2006
Abstract Nasal polyposis is a very common and multifactorial disease. Whereas eosinophil-dominated polyps often are sensitive to antiinflammatory treatment like corticosteroids, the therapy of polyps without eosinophils is more difficult and disappointing. We report the clinical course of a 29-year-old albino patient suffering from a extreme manifestation of Woakes’ syndrome, which is characterized by severe recurrent nasal polyps, often without eosinophils on histological examination and with broadening of the nose. In this case, the recurrent fibrotic polyps without eosinophils were resistant to conventional medical and surgical treatment and required further treatment with radiotherapy with awareness of all possible future sequelae. The pathoetiology and treatment of Woakes’ syndrome as well as of albinism were discussed. # 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Woakes; Albinism; Nasal polyps; Radiotherapy
1. Introduction The occurrence of nasal polyps is a multifactorial disease resulting from chronic immune inflammatory processes within the paranasal sinuses. The pathophysiological processes of the underlying inflammation causing chronic hyperplastic sinusitis and nasal polyposis are still unclear. Recently, an eosinophilic-dominated (e.g., aspirin intolerance, allergy) and a non-eosinophilic inflammation (e.g., cystic fibrosis, primary ciliary dyskinesia) of the polyps have been distinguished. Generally, eosinophilic-dominated polyps are more responsive to anti-inflammatory treatment and the non-eosinophilic-dominated polyps are more responsive to surgical procedures [1]. Extensive polyp growth in the paranasal sinuses can lead to bone erosion of the sinus walls and cause facial disfigurement due to continuous pressure or chronic inflammation. This phenomenon is called Woakes’ syndrome or ethmoiditis and was first described by Woakes in 1885 [2]. The clinical hallmark of this entity with severe * Corresponding author. Tel.: +41 31 632 29 41; fax: +41 31 632 49 00. E-mail address: [email protected] (M. Caversaccio).
recurrent growth of nasal polyposis is broadening of the nose and hypertelorism. The syndrome has also been described with bronchiectasis in children [3]. Polyps in Woakes’ syndrome do not differ histological from banal polyps but are more often caused by a non-eosinophilic-dominated inflammation [4]. Albinism is a very rare disease. The association of albinism and Woakes’ syndrome is not reported in the world literature. The difficult treatment modality ending with radiotherapy will be described.
2. Case report A 29-year-old albino-black man from Nigeria suffered from chronic rhinosinusitis with recurrent and massive nasal polyposis since the age of 9 years with consequently progressive asymmetry of the face with broadening of the nose and hypertelorism (Fig. 1). Surgery of the nasal polyps was performed two times in Nigeria. A few months after each surgical intervention, nasal obstruction worsened again. He was a non-smoker and had no history of allergies. In the family, there was an albino uncle, but there were no histories of polyps or allergies.
0385-8146/$ – see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2006.09.030
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M. Caversaccio et al. / Auris Nasus Larynx 34 (2007) 245–248
Fig. 1. On the left side is the young patient’s face with a small nose and a normal configuration at age of 6 years. The right picture shows the patients face at the age of 29 years; he shows a much more broadened nose.
The physical examination revealed an albino black man in good health with hypertelorism and bilateral pendular nystagmus. The nose was extremely broadened with bilateral enlargement of the nasal pyramid of 7 cm. Anterior rhinoscopy showed massive nasal polyps obstructing all of the cavum and the entire vestibulum nasi on both sides (Fig. 2). Ophthalmologic examination attested to pale irises and a decreased visus of 0.3 dioptries on both sides with normal orbital pressure and no signs of optic nerve compression. Fundoscopy disclosed a retina lacking melanin pigment, as seen in the albino population. CT scan showed a complete obliteration of the paranasal sinuses on both sides with a bulging of the ethmoid walls into the orbits. Laboratory analyses were normal for eosinophils, eosinophilic cationic protein, C-reacting protein, complete blood cell counts, thyroid function, serum protein electrophoresis, antinuclear antibody, antineutrophilic cytoplasmatic
antibody assays and rheumatoid factors. Serological tests for various infectious agents such as Treponema pallidum, Human papilloma virus and HIV as well as a tuberculin skin test were also negative. An allergologic work-up did not reveal any sensitization to common inhalants and fungal antigens by prick tests and/or serum specific IgE antibodies. Complete spirometry and chest X-ray were normal, without any indication for bronchiectasis. Histology of the polyps showed squamous epithelium partially covered by respiratory mucosa with a moderate chronic inflammation and focal fibrosis but without eosinophils (Fig. 3). The molecular-genetic DNA analysis demonstrated no mutation in the GFTR gene, whereby cystic fibrosis could be excluded. Treatment and clinical course: oral corticosteroids (prednisonum 50 mg per day), montelucast (10 mg per day) and a topical nasal steroid (200 mg mometason) were used continuously for 12 weeks, followed by a 2-week antibiotic treatment with amoxicillin/clavulanic acid (1 g twice a day) but without any clinical improvement. Local antifungal treatment with an amphotericin B spray (concentration 10 mg/ml; 2 2 pushes/day [=4 mg of amphotericin B] for each nose) showed no effect on the polyp size. Endonasal polypectomy with fronto-spheno-ethmoidectomy and maxillary sinus fenestration was performed after 3 months. Although post-operative treatment with oral and topical corticosteroids was started, the polyps grew again and filled out the cavum nasi completely within only 3 weeks after surgery. Because conventional medical and surgical treatment was ineffective, a radiation concept was chosen, to which the patient gave his informed consent. Percutaneous radiation of the cavum nasi and the paranasal sinuses was started with an initial dose of 200 cGy and a total dose of 5000 cGy in 35 fractions during 35 days was applied. The radiation was well tolerated by the patient without any side effects and during a monthly follow-up, the polyps showed a continuous regression. Three years after radiotherapy, the patient shows a stable polyposis grade I on both sides, according to the polyp staging of Malm (Fig. 3) [5]. The patient is free from headaches and rhinorrhea and is again breathing well through the nose.
3. Discussion
Fig. 2. Polyps fill up the whole vestibulum and reach the columella of the nose. The nasal pyramid is bilaterally enlarged up to 7 cm visible also on the 3D CT reconstruction. Intraoperative navigation view and CT 3 years after surgery and radiotherapy.
Woakes’ syndrome was first reported based on a case in 1885 by Dr. E. Woakes. It was defined as ‘‘necrotising ethmoiditis’’ and nasal polyps with broadening of the nose [2]. After observations by other authors, the syndrome was defined in 1923 by the ‘‘Socie´te´ franc¸aise de laryngologie’’ by the following four characteristics [6]: (1) bilateral nasal polyps in the middle meatus beginning during childhood, (2) ethmoiditis, (3) hypertrophic process with nasal pyramid deformation and (4) therapeutic failure with constant and rapid recurrences. The pathoetiology of
M. Caversaccio et al. / Auris Nasus Larynx 34 (2007) 245–248
247
Fig. 3. CT and histopathology of nasal polyps, before (a) and after (b) radiation therapy. Decreased sinus hypodensities (ethmoid and frontal) 4 months after radiotherapy. Histological examination with hematoxylin-eosin 40: Squamous epithelium with (a) lacunae surrounded by myofibroblasts, but without eosinophils. (b) Chronic inflammation with increasing of fibroblasts, but diminished lacunae.
this syndrome is still unknown. Various authors have discussed genetic factors, as the syndrome has occurred more frequently among sisters, as well as an infectious origin, primarily syphilitic [7]. Busca discussed external noxious agents and allergies, accelerating the growth of polyps [7]. However, in many cases, no agent or allergy could be found. This indicates that the syndrome with its deforming and recurrent polyps is only a clinical entity. Also in our case we could not find any real pathoetiology. The extreme broadening of the nose in our patient is explained by the chronic pressure of the polyps. The chronic pressure also leads to a bolding of the lamina papyracea with progressive protrusio bulbi to the lateral side of the eye and to a risk of slowly progressing blindness due to compression of the optic nerve. From a histological approach our patient showed a chronic inflammatory or fibrotic without eosinophils [8]. Fibrotic types of polyps are known to be difficult to treat, what can be the reason for medical-therapeutic failure. In our case, an anti-inflammatory therapy with prednisonum as well as a local antifungal treatment with amphothericin B nasal spray could not influence the aggressive polyp growth. Interferone, being only effective in eosinophilic polyps by down regulating IL-5 synthesis, was not applied for this reason [9]. Methotrexat was not given because of unusual reactions of our patient to several drugs administered during surgery. Finally, we chose the unusual ‘‘obsolete’’ radio-
therapeutic approach, knowing the possible future sequelae for cataract and carcinogenesis. This treatment was well tolerated and proved to be effective in our case (follow-up 3 years). The possible mechanism of radiotherapy consists of destruction and inflammation with diminished wateralbumin content in the polyps and consequently thickness of the stroma and membrane with fibronectine from fibroblasts. This condition is no more favourable for polyp formation. A further remarkable fact is that our patient was an albino black man. Albinism is composed of a heterogeneous group of disorders of the melanin biosynthesis pathway with hypopigmentation of the skin, hair and eyes and is well known among South African black people [10]. The most common form in black people is the tyrosinase-positive oculocutaneous albinism (OAC2), an autosomal recessive disorder with a prevalence of 1:3900 individuals [10]. This form is frequently associated with a congenital x-linked nystagmus and reduced visus, as seen in our patient, as well as with further syndromes [11]. Albinism is often seen in patients with polyglandular autoimmunopathies such as juvenile diabetes mellitus. We could find no relationship between albinism and polyps in the literature, and to date no case of albinism with nasal polyps and Woakes’ syndrome has been published. If the combination of albinism and polyps is coincidental or if there is a control gene link, remain unclear.
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M. Caversaccio et al. / Auris Nasus Larynx 34 (2007) 245–248
References [1] Van der Baan B. Epidemiology and natural history. In: Mygind N, Lildholdt T, editors. In nasal polyps—an inflammatory disease and its treatment. Copenhagen: Munksgaard; 1997. p. 13–5. [2] Woakes E. Necrotising ethmoiditis and mucous polyps. Lancet 1885;61:619. [3] Kellerhals B, Uthemann B. Woakes’ syndrome: the problems of infantile nasal polyps. Int J Pediatr Otorhinolaryngol 1979;1:79–85. [4] Appaix S, Robert J. Polypose de´formante et re´cidivante des jeunes (maladie de Woakes). Rev Laryngol 1953;74:216–54. [5] Malm L. Assessment and staging of nasal polyposis. Acta Otolaryngol (Stockh) 1997;117:465–7. [6] Canuyt M, Terracol J. La polypose nasal re´cidivante et de´formante des jeunes. Rev Laryng Otol 1924;45:7–10.
[7] Busca GP. The Woakes’ syndrome. Ethiopathogenetic and clinical considerations with personal case report. Minerva Otorinolaringol 1966;16:201–5. [8] Pawankar R. Nasal polyposis: an update. Curr Opin Allergy Clin Immunol 2003;3:1–6. [9] Huber MA, Gall H, Getho¨ffer K, Muhlmeier G, Maier H, Peter RU. Sucessful prevention of recurrent nasal polyps by means of systemic low dose IFN-alpha 2a. J Allergy Clin Immunol 2001;108:141. [10] Kerr R, Stevens G, Manga P, Salm S, John P, Haw T, et al. Identification of P-gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa. Hum Mutat 2000;15:166–72. [11] Preising M, Op de Laak JP, Lorenz B. Deletion in the OA1 gene in family with congenital X linked nystagmus. Br J Ophthalmol 2001;85:1098–103.
Woakes’ syndrome and albinism Marco Caversaccio a,*, Ariane Baumann a, Arthur Helbling b a
b
Department of ENT, Head and Neck Surgery, University Hospital, Inselspital, 3010 Bern, Switzerland Department of Policlinics of Allergology and Clinical Immunology, Inselspital, University of Bern, Switzerland Received 4 July 2006; accepted 25 September 2006 Available online 19 December 2006
Abstract Nasal polyposis is a very common and multifactorial disease. Whereas eosinophil-dominated polyps often are sensitive to antiinflammatory treatment like corticosteroids, the therapy of polyps without eosinophils is more difficult and disappointing. We report the clinical course of a 29-year-old albino patient suffering from a extreme manifestation of Woakes’ syndrome, which is characterized by severe recurrent nasal polyps, often without eosinophils on histological examination and with broadening of the nose. In this case, the recurrent fibrotic polyps without eosinophils were resistant to conventional medical and surgical treatment and required further treatment with radiotherapy with awareness of all possible future sequelae. The pathoetiology and treatment of Woakes’ syndrome as well as of albinism were discussed. # 2006 Elsevier Ireland Ltd. All rights reserved. Keywords: Woakes; Albinism; Nasal polyps; Radiotherapy
1. Introduction The occurrence of nasal polyps is a multifactorial disease resulting from chronic immune inflammatory processes within the paranasal sinuses. The pathophysiological processes of the underlying inflammation causing chronic hyperplastic sinusitis and nasal polyposis are still unclear. Recently, an eosinophilic-dominated (e.g., aspirin intolerance, allergy) and a non-eosinophilic inflammation (e.g., cystic fibrosis, primary ciliary dyskinesia) of the polyps have been distinguished. Generally, eosinophilic-dominated polyps are more responsive to anti-inflammatory treatment and the non-eosinophilic-dominated polyps are more responsive to surgical procedures [1]. Extensive polyp growth in the paranasal sinuses can lead to bone erosion of the sinus walls and cause facial disfigurement due to continuous pressure or chronic inflammation. This phenomenon is called Woakes’ syndrome or ethmoiditis and was first described by Woakes in 1885 [2]. The clinical hallmark of this entity with severe * Corresponding author. Tel.: +41 31 632 29 41; fax: +41 31 632 49 00. E-mail address: [email protected] (M. Caversaccio).
recurrent growth of nasal polyposis is broadening of the nose and hypertelorism. The syndrome has also been described with bronchiectasis in children [3]. Polyps in Woakes’ syndrome do not differ histological from banal polyps but are more often caused by a non-eosinophilic-dominated inflammation [4]. Albinism is a very rare disease. The association of albinism and Woakes’ syndrome is not reported in the world literature. The difficult treatment modality ending with radiotherapy will be described.
2. Case report A 29-year-old albino-black man from Nigeria suffered from chronic rhinosinusitis with recurrent and massive nasal polyposis since the age of 9 years with consequently progressive asymmetry of the face with broadening of the nose and hypertelorism (Fig. 1). Surgery of the nasal polyps was performed two times in Nigeria. A few months after each surgical intervention, nasal obstruction worsened again. He was a non-smoker and had no history of allergies. In the family, there was an albino uncle, but there were no histories of polyps or allergies.
0385-8146/$ – see front matter # 2006 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.anl.2006.09.030
246
M. Caversaccio et al. / Auris Nasus Larynx 34 (2007) 245–248
Fig. 1. On the left side is the young patient’s face with a small nose and a normal configuration at age of 6 years. The right picture shows the patients face at the age of 29 years; he shows a much more broadened nose.
The physical examination revealed an albino black man in good health with hypertelorism and bilateral pendular nystagmus. The nose was extremely broadened with bilateral enlargement of the nasal pyramid of 7 cm. Anterior rhinoscopy showed massive nasal polyps obstructing all of the cavum and the entire vestibulum nasi on both sides (Fig. 2). Ophthalmologic examination attested to pale irises and a decreased visus of 0.3 dioptries on both sides with normal orbital pressure and no signs of optic nerve compression. Fundoscopy disclosed a retina lacking melanin pigment, as seen in the albino population. CT scan showed a complete obliteration of the paranasal sinuses on both sides with a bulging of the ethmoid walls into the orbits. Laboratory analyses were normal for eosinophils, eosinophilic cationic protein, C-reacting protein, complete blood cell counts, thyroid function, serum protein electrophoresis, antinuclear antibody, antineutrophilic cytoplasmatic
antibody assays and rheumatoid factors. Serological tests for various infectious agents such as Treponema pallidum, Human papilloma virus and HIV as well as a tuberculin skin test were also negative. An allergologic work-up did not reveal any sensitization to common inhalants and fungal antigens by prick tests and/or serum specific IgE antibodies. Complete spirometry and chest X-ray were normal, without any indication for bronchiectasis. Histology of the polyps showed squamous epithelium partially covered by respiratory mucosa with a moderate chronic inflammation and focal fibrosis but without eosinophils (Fig. 3). The molecular-genetic DNA analysis demonstrated no mutation in the GFTR gene, whereby cystic fibrosis could be excluded. Treatment and clinical course: oral corticosteroids (prednisonum 50 mg per day), montelucast (10 mg per day) and a topical nasal steroid (200 mg mometason) were used continuously for 12 weeks, followed by a 2-week antibiotic treatment with amoxicillin/clavulanic acid (1 g twice a day) but without any clinical improvement. Local antifungal treatment with an amphotericin B spray (concentration 10 mg/ml; 2 2 pushes/day [=4 mg of amphotericin B] for each nose) showed no effect on the polyp size. Endonasal polypectomy with fronto-spheno-ethmoidectomy and maxillary sinus fenestration was performed after 3 months. Although post-operative treatment with oral and topical corticosteroids was started, the polyps grew again and filled out the cavum nasi completely within only 3 weeks after surgery. Because conventional medical and surgical treatment was ineffective, a radiation concept was chosen, to which the patient gave his informed consent. Percutaneous radiation of the cavum nasi and the paranasal sinuses was started with an initial dose of 200 cGy and a total dose of 5000 cGy in 35 fractions during 35 days was applied. The radiation was well tolerated by the patient without any side effects and during a monthly follow-up, the polyps showed a continuous regression. Three years after radiotherapy, the patient shows a stable polyposis grade I on both sides, according to the polyp staging of Malm (Fig. 3) [5]. The patient is free from headaches and rhinorrhea and is again breathing well through the nose.
3. Discussion
Fig. 2. Polyps fill up the whole vestibulum and reach the columella of the nose. The nasal pyramid is bilaterally enlarged up to 7 cm visible also on the 3D CT reconstruction. Intraoperative navigation view and CT 3 years after surgery and radiotherapy.
Woakes’ syndrome was first reported based on a case in 1885 by Dr. E. Woakes. It was defined as ‘‘necrotising ethmoiditis’’ and nasal polyps with broadening of the nose [2]. After observations by other authors, the syndrome was defined in 1923 by the ‘‘Socie´te´ franc¸aise de laryngologie’’ by the following four characteristics [6]: (1) bilateral nasal polyps in the middle meatus beginning during childhood, (2) ethmoiditis, (3) hypertrophic process with nasal pyramid deformation and (4) therapeutic failure with constant and rapid recurrences. The pathoetiology of
M. Caversaccio et al. / Auris Nasus Larynx 34 (2007) 245–248
247
Fig. 3. CT and histopathology of nasal polyps, before (a) and after (b) radiation therapy. Decreased sinus hypodensities (ethmoid and frontal) 4 months after radiotherapy. Histological examination with hematoxylin-eosin 40: Squamous epithelium with (a) lacunae surrounded by myofibroblasts, but without eosinophils. (b) Chronic inflammation with increasing of fibroblasts, but diminished lacunae.
this syndrome is still unknown. Various authors have discussed genetic factors, as the syndrome has occurred more frequently among sisters, as well as an infectious origin, primarily syphilitic [7]. Busca discussed external noxious agents and allergies, accelerating the growth of polyps [7]. However, in many cases, no agent or allergy could be found. This indicates that the syndrome with its deforming and recurrent polyps is only a clinical entity. Also in our case we could not find any real pathoetiology. The extreme broadening of the nose in our patient is explained by the chronic pressure of the polyps. The chronic pressure also leads to a bolding of the lamina papyracea with progressive protrusio bulbi to the lateral side of the eye and to a risk of slowly progressing blindness due to compression of the optic nerve. From a histological approach our patient showed a chronic inflammatory or fibrotic without eosinophils [8]. Fibrotic types of polyps are known to be difficult to treat, what can be the reason for medical-therapeutic failure. In our case, an anti-inflammatory therapy with prednisonum as well as a local antifungal treatment with amphothericin B nasal spray could not influence the aggressive polyp growth. Interferone, being only effective in eosinophilic polyps by down regulating IL-5 synthesis, was not applied for this reason [9]. Methotrexat was not given because of unusual reactions of our patient to several drugs administered during surgery. Finally, we chose the unusual ‘‘obsolete’’ radio-
therapeutic approach, knowing the possible future sequelae for cataract and carcinogenesis. This treatment was well tolerated and proved to be effective in our case (follow-up 3 years). The possible mechanism of radiotherapy consists of destruction and inflammation with diminished wateralbumin content in the polyps and consequently thickness of the stroma and membrane with fibronectine from fibroblasts. This condition is no more favourable for polyp formation. A further remarkable fact is that our patient was an albino black man. Albinism is composed of a heterogeneous group of disorders of the melanin biosynthesis pathway with hypopigmentation of the skin, hair and eyes and is well known among South African black people [10]. The most common form in black people is the tyrosinase-positive oculocutaneous albinism (OAC2), an autosomal recessive disorder with a prevalence of 1:3900 individuals [10]. This form is frequently associated with a congenital x-linked nystagmus and reduced visus, as seen in our patient, as well as with further syndromes [11]. Albinism is often seen in patients with polyglandular autoimmunopathies such as juvenile diabetes mellitus. We could find no relationship between albinism and polyps in the literature, and to date no case of albinism with nasal polyps and Woakes’ syndrome has been published. If the combination of albinism and polyps is coincidental or if there is a control gene link, remain unclear.
248
M. Caversaccio et al. / Auris Nasus Larynx 34 (2007) 245–248
References [1] Van der Baan B. Epidemiology and natural history. In: Mygind N, Lildholdt T, editors. In nasal polyps—an inflammatory disease and its treatment. Copenhagen: Munksgaard; 1997. p. 13–5. [2] Woakes E. Necrotising ethmoiditis and mucous polyps. Lancet 1885;61:619. [3] Kellerhals B, Uthemann B. Woakes’ syndrome: the problems of infantile nasal polyps. Int J Pediatr Otorhinolaryngol 1979;1:79–85. [4] Appaix S, Robert J. Polypose de´formante et re´cidivante des jeunes (maladie de Woakes). Rev Laryngol 1953;74:216–54. [5] Malm L. Assessment and staging of nasal polyposis. Acta Otolaryngol (Stockh) 1997;117:465–7. [6] Canuyt M, Terracol J. La polypose nasal re´cidivante et de´formante des jeunes. Rev Laryng Otol 1924;45:7–10.
[7] Busca GP. The Woakes’ syndrome. Ethiopathogenetic and clinical considerations with personal case report. Minerva Otorinolaringol 1966;16:201–5. [8] Pawankar R. Nasal polyposis: an update. Curr Opin Allergy Clin Immunol 2003;3:1–6. [9] Huber MA, Gall H, Getho¨ffer K, Muhlmeier G, Maier H, Peter RU. Sucessful prevention of recurrent nasal polyps by means of systemic low dose IFN-alpha 2a. J Allergy Clin Immunol 2001;108:141. [10] Kerr R, Stevens G, Manga P, Salm S, John P, Haw T, et al. Identification of P-gene mutations in individuals with oculocutaneous albinism in sub-Saharan Africa. Hum Mutat 2000;15:166–72. [11] Preising M, Op de Laak JP, Lorenz B. Deletion in the OA1 gene in family with congenital X linked nystagmus. Br J Ophthalmol 2001;85:1098–103.