Case for Diagnosis DOI: 10.1111/ddg.12223
Erythematous swollen ears
Bruno de Oliveira Rocha, Tarsila Carvalho dos Santos, Juliana Dumêt Fernandes Department of Dermatology, Federal University of Bahia, Salvador, Bahia, Brazil
History
Her ears were painful and warm. Audiometry showed mild sensorineural deafness. Laboratory assessment for anti-type II collagen antibody was negative. Thyroid-stimulating hormone was slightly reduced, with normal T3 and free T4 levels. Others complementary exams, including chest x-ray, echocardiogram, complete blood count, ESR and CRP were all within normal limits. Histology of the ear revealed a perichondrial infiltrate rich in lymphocytes and plasma cells, as well as focal decreased basophilia of cartilage (Figure 2a–c).
A 39-years-old woman presented with a 10-months history of recurrent swelling and burning in the ears, with accompanying progressive hearing impairment, weight loss and some episodes of fever. Physical examination revealed erythema and swelling of the ears, sparing the earlobes (Figure 1).
Figure 1 Erythema and swelling of the right (a) and left (b) ear, with sparing of the earlobes.
Figure 2 Histology shows an inflammatory infiltrate of lymphocytes, plasma cells, and a few neutrophils, which is accentuated in the perichondrial region and penetrates into the cartilage (Hematoxylin and eosin stain, original magnification x100) (a). Closer views (b, c) of the inflammatory infiltrate (Hematoxylin and eosin stain, original magnification x250 [b], x400 [c]).
What’s your diagnosis?
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1203
269
Case for Diagnosis Diagnosis: Relapsing polychondritis (RP)
Discussion Relapsing polychondritis is a rare chronic inflammatory disorder, first described by Jaksch-Wartenhorst (1923), who called it “polychondropathia” [1–3]. Because of its episodic nature, it was later renamed [1]. Males and females are equally affected and its onset usually begins between 20–60 years, with a peak of incidence in the fourth decade [4, 5], as seen in our patient. Autoimmune mechanisms are the most likely cause of RP [1–3, 6, 7]. Anti-type II collagen antibodies were not found in our patient, but they are only observed in 50% of patients [1, 3, 8], and correlate with the disease severity [2]. Granular deposits of immunoglobulins at fibrochondrial junctions also indicate that immune-complex deposits may play a role in this condition [1, 3]. The clinical criteria for diagnosing RP were proposed by McAdams [5]: (1) bilateral auricular chondritis; (2) nasal chondritis; (3) respiratory tract chondritis; (4) seronegative, non-erosive polyarthritis; (5) ocular inflammation; (6) audiovestibular lesions. In the presence of characteristic histopathological findings, one clinical criterion is sufficient to make the diagnosis [3–5]. Our patient had the criteria (1) and (6). Non-specific symptoms as fever and weight loss, as seen in our case, can be present [2, 8]. Most patients have more than two sites of involvement, but the disease can be limited to one site for years [1, 4, 5]. Auricular impairment is the most prominent clinical feature of RP (85%) [1–7], followed by injuries in joints, nasal cartilage, ocular tissues, respiratory tract and hearts valves [1, 5–9]. During the acute stage, the affected ear is red, tender and swollen [1, 2]. The fact that RP spares the earlobe, as seen in our patient, makes this disease easily distinguishable from cellulitis [1, 2, 9]. Clinical overlaps between RP and granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) may be identified by determination of anti-proteinase-3 antibodies (c-ANCA) [2, 3]. Respiratory tract involvement leads to impaired breathing and recurrent infections [1, 2]. Damage to the cardiac valves can result in sudden valve rupture, even in patients in remission [1, 4]. Ophthalmologic involvement occurs in 60–65% of cases [1, 2], mainly episcleritis, conjunctivitis and iritis [1, 6, 8]. Hearing impairment can be both bilateral and unilateral, with a sudden or progressive onset, and arising due to the damage to the eighth cranial nerve alone or combined with stenosis of the external auditory canal [7, 8]. Nerve damage probably stems from the internal auditory artery vasculitis, which can also cause vertigo, imbalance, and
270
dizziness [7]. Hearing loss is usually permanent, while vestibular disorders tend to subside [3, 8]. Among these systemic manifestations, our patient only had hearing loss. Typical histopathology of RP shows areas of decreased basophilia (damaged cartilage) accompanied by an infiltrate dominated by lymphocytes and plasma cells which is perichondrial and may penetrate into the cartilage [1–10]. After many relapses, fragments of cartilage are surrounded and replaced by granulation tissue [1, 3]. In our case, the microscopic picture was classic. The disease course is extremely variable, and relapses may vary in frequency and severity [1, 4]. Almost all the information about treatment come from retrospective analysis of isolated case reports and small case series [1, 2, 4–8, 10]. The progression of an acute relapse can be controlled with corticosteroids, which remains the mainstay of therapy [1, 3, 4]. Colchicine has particular benefit for isolated auricular chondritis. Dapsone is an option for mild RP, but side effects are frequent. Methotrexate and azathioprine have been used as steroid-sparing agents. In cases of severe pulmonary, renal and cardiac disease, the best option is cyclophosphamide. Cyclosporin A can be useful in cases unresponsive to other treatments [1–3, 10]. The use of intravenous immunoglobulins, anti-TNFa therapies and IL-1 receptor antagonist were also reported [1, 10]. Our patient experienced great improvement with prednisone in the acute stage followed by the use of azathioprine to prevent relapses. We stress that, although a rare disease, RP must be considered as a possible differential diagnosis of an erythematous swelling ear, since the precocious and aggressive treatment will surely delay or prevent cartilage destruction [3, 6, 8]. Conflict of interest None. Correspondence to Juliana Dumêt Fernandes, MD, PhD Dr. João Garcez Fróes Street, 122, Room 101 Ondina, Salvador, Bahia 40170-040, Brazil E-mail: [email protected]
References 1
2
Burrows NP, Lovell CR. Disorders of Connective Tissue. In: Burns T, Breathnach S, Cox N, Griffiths C, eds: Rook’s Textbook of Dermatology. 8th edn. Oxford: Blackwell Publishing, 2010: 45.42–45.44. Frances C. Relapsing Polychondritis. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ: Fitzpatrick’s Dermatology in General Medicine. 7th edn. New York: McGrall-Hill, 2008; 1567–9.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1203
Case for Diagnosis
3 4 5
6
Kent PD, Michet CJJ, Luthra HS. Relapsing polychondritis. Curr Opin Rheumatol 2004; 16(1): 56–61. Herrera I, Mannoni A, Altman RD. Relapsing polychondritis: commentary. Reumatismo 2002; 54(4): 301–6. McAdam LP, O’Hanlan MA, Bluestone R, Pearson CM. Relapsing Polychondritis: Prospective study of 23 patients and a review of the literature. Medicine (Baltimore) 1976; 55(3): 193–215. Letko E, Zafirakis P, Baltatzis S, et al. Relapsing polychondritis: a clinical review. Semin Arthritis Rheum. 2002; 31(6): 384–95.
7
Edrees A. Relapsing polychondritis: a description of a case and review article. Rheumatol Int 2011; 31(6): 707–13. 8 Chopra R, Chaudhary N, Kay J. Relapsing polychondritis. Rheum Dis Clin North Am 2013; 39(2): 263–76. 9 Krumbholz A, Heinemann C, Ziemer M, et al. Rezidivierende Polychondritis als seltene Differentialdiagnose des Erysipels. J Dtsch Dermatol Ges 2004; 2(4): 286–9. 10 McCarthy EM, Cunnane G. Treatment of relapsing polychondritis in the era of biological agents. Rheumatol Int 2010; 30(6): 827–8.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1203
271
Erythematous swollen ears
Bruno de Oliveira Rocha, Tarsila Carvalho dos Santos, Juliana Dumêt Fernandes Department of Dermatology, Federal University of Bahia, Salvador, Bahia, Brazil
History
Her ears were painful and warm. Audiometry showed mild sensorineural deafness. Laboratory assessment for anti-type II collagen antibody was negative. Thyroid-stimulating hormone was slightly reduced, with normal T3 and free T4 levels. Others complementary exams, including chest x-ray, echocardiogram, complete blood count, ESR and CRP were all within normal limits. Histology of the ear revealed a perichondrial infiltrate rich in lymphocytes and plasma cells, as well as focal decreased basophilia of cartilage (Figure 2a–c).
A 39-years-old woman presented with a 10-months history of recurrent swelling and burning in the ears, with accompanying progressive hearing impairment, weight loss and some episodes of fever. Physical examination revealed erythema and swelling of the ears, sparing the earlobes (Figure 1).
Figure 1 Erythema and swelling of the right (a) and left (b) ear, with sparing of the earlobes.
Figure 2 Histology shows an inflammatory infiltrate of lymphocytes, plasma cells, and a few neutrophils, which is accentuated in the perichondrial region and penetrates into the cartilage (Hematoxylin and eosin stain, original magnification x100) (a). Closer views (b, c) of the inflammatory infiltrate (Hematoxylin and eosin stain, original magnification x250 [b], x400 [c]).
What’s your diagnosis?
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1203
269
Case for Diagnosis Diagnosis: Relapsing polychondritis (RP)
Discussion Relapsing polychondritis is a rare chronic inflammatory disorder, first described by Jaksch-Wartenhorst (1923), who called it “polychondropathia” [1–3]. Because of its episodic nature, it was later renamed [1]. Males and females are equally affected and its onset usually begins between 20–60 years, with a peak of incidence in the fourth decade [4, 5], as seen in our patient. Autoimmune mechanisms are the most likely cause of RP [1–3, 6, 7]. Anti-type II collagen antibodies were not found in our patient, but they are only observed in 50% of patients [1, 3, 8], and correlate with the disease severity [2]. Granular deposits of immunoglobulins at fibrochondrial junctions also indicate that immune-complex deposits may play a role in this condition [1, 3]. The clinical criteria for diagnosing RP were proposed by McAdams [5]: (1) bilateral auricular chondritis; (2) nasal chondritis; (3) respiratory tract chondritis; (4) seronegative, non-erosive polyarthritis; (5) ocular inflammation; (6) audiovestibular lesions. In the presence of characteristic histopathological findings, one clinical criterion is sufficient to make the diagnosis [3–5]. Our patient had the criteria (1) and (6). Non-specific symptoms as fever and weight loss, as seen in our case, can be present [2, 8]. Most patients have more than two sites of involvement, but the disease can be limited to one site for years [1, 4, 5]. Auricular impairment is the most prominent clinical feature of RP (85%) [1–7], followed by injuries in joints, nasal cartilage, ocular tissues, respiratory tract and hearts valves [1, 5–9]. During the acute stage, the affected ear is red, tender and swollen [1, 2]. The fact that RP spares the earlobe, as seen in our patient, makes this disease easily distinguishable from cellulitis [1, 2, 9]. Clinical overlaps between RP and granulomatosis with polyangiitis (formerly known as Wegener granulomatosis) may be identified by determination of anti-proteinase-3 antibodies (c-ANCA) [2, 3]. Respiratory tract involvement leads to impaired breathing and recurrent infections [1, 2]. Damage to the cardiac valves can result in sudden valve rupture, even in patients in remission [1, 4]. Ophthalmologic involvement occurs in 60–65% of cases [1, 2], mainly episcleritis, conjunctivitis and iritis [1, 6, 8]. Hearing impairment can be both bilateral and unilateral, with a sudden or progressive onset, and arising due to the damage to the eighth cranial nerve alone or combined with stenosis of the external auditory canal [7, 8]. Nerve damage probably stems from the internal auditory artery vasculitis, which can also cause vertigo, imbalance, and
270
dizziness [7]. Hearing loss is usually permanent, while vestibular disorders tend to subside [3, 8]. Among these systemic manifestations, our patient only had hearing loss. Typical histopathology of RP shows areas of decreased basophilia (damaged cartilage) accompanied by an infiltrate dominated by lymphocytes and plasma cells which is perichondrial and may penetrate into the cartilage [1–10]. After many relapses, fragments of cartilage are surrounded and replaced by granulation tissue [1, 3]. In our case, the microscopic picture was classic. The disease course is extremely variable, and relapses may vary in frequency and severity [1, 4]. Almost all the information about treatment come from retrospective analysis of isolated case reports and small case series [1, 2, 4–8, 10]. The progression of an acute relapse can be controlled with corticosteroids, which remains the mainstay of therapy [1, 3, 4]. Colchicine has particular benefit for isolated auricular chondritis. Dapsone is an option for mild RP, but side effects are frequent. Methotrexate and azathioprine have been used as steroid-sparing agents. In cases of severe pulmonary, renal and cardiac disease, the best option is cyclophosphamide. Cyclosporin A can be useful in cases unresponsive to other treatments [1–3, 10]. The use of intravenous immunoglobulins, anti-TNFa therapies and IL-1 receptor antagonist were also reported [1, 10]. Our patient experienced great improvement with prednisone in the acute stage followed by the use of azathioprine to prevent relapses. We stress that, although a rare disease, RP must be considered as a possible differential diagnosis of an erythematous swelling ear, since the precocious and aggressive treatment will surely delay or prevent cartilage destruction [3, 6, 8]. Conflict of interest None. Correspondence to Juliana Dumêt Fernandes, MD, PhD Dr. João Garcez Fróes Street, 122, Room 101 Ondina, Salvador, Bahia 40170-040, Brazil E-mail: [email protected]
References 1
2
Burrows NP, Lovell CR. Disorders of Connective Tissue. In: Burns T, Breathnach S, Cox N, Griffiths C, eds: Rook’s Textbook of Dermatology. 8th edn. Oxford: Blackwell Publishing, 2010: 45.42–45.44. Frances C. Relapsing Polychondritis. In: Wolff K, Goldsmith LA, Katz SI, Gilchrest BA, Paller AS, Leffell DJ: Fitzpatrick’s Dermatology in General Medicine. 7th edn. New York: McGrall-Hill, 2008; 1567–9.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1203
Case for Diagnosis
3 4 5
6
Kent PD, Michet CJJ, Luthra HS. Relapsing polychondritis. Curr Opin Rheumatol 2004; 16(1): 56–61. Herrera I, Mannoni A, Altman RD. Relapsing polychondritis: commentary. Reumatismo 2002; 54(4): 301–6. McAdam LP, O’Hanlan MA, Bluestone R, Pearson CM. Relapsing Polychondritis: Prospective study of 23 patients and a review of the literature. Medicine (Baltimore) 1976; 55(3): 193–215. Letko E, Zafirakis P, Baltatzis S, et al. Relapsing polychondritis: a clinical review. Semin Arthritis Rheum. 2002; 31(6): 384–95.
7
Edrees A. Relapsing polychondritis: a description of a case and review article. Rheumatol Int 2011; 31(6): 707–13. 8 Chopra R, Chaudhary N, Kay J. Relapsing polychondritis. Rheum Dis Clin North Am 2013; 39(2): 263–76. 9 Krumbholz A, Heinemann C, Ziemer M, et al. Rezidivierende Polychondritis als seltene Differentialdiagnose des Erysipels. J Dtsch Dermatol Ges 2004; 2(4): 286–9. 10 McCarthy EM, Cunnane G. Treatment of relapsing polychondritis in the era of biological agents. Rheumatol Int 2010; 30(6): 827–8.
© 2014 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd. | JDDG | 1610-0379/2014/1203
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