CED
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
A case of mistaken identity: unilateral erythema elevatum diutinum associated with IgA paraproteinaemia C. L. Thomas, L. Ffolkes and V. Akhras Department of Dermatology, St George’s Hospital, London, UK doi:10.1111/ced.12622
Summary
We report the case of a 27-year-old woman presenting with unilateral painless nodules of the left hand following trauma. Initially diagnosed as nontuberculous mycobacterium infection and treated with prolonged courses of antibiotics with little improvement, the condition was subsequently diagnosed histologically as erythema elevatum diutinum (EED). The lesion was treated with surgical excision, and the patient remained lesion-free at the 1-year follow-up. Although the lesion was otherwise asymptomatic, further investigation demonstrated an underlying IgA paraproteinaemia. This case should alert physicians to consider the diagnosis of EED in a unilateral presentation, and highlights the importance of investigation for underlying associated haematological disease.
Erythema elevatum diutinum (EED) is a rare chronic form of cutaenous vasculitis, which falls within the subgroup of neutrophilic dermatoses (also including Sweet syndrome and pyoderma gangrenosum). Clinically, the presentation of EED is diverse. It is characterized by the presence of plaques, papules or nodules, which may be erythematous, brown or violaceous in colour.1 Atypical presentations, such as vesiculobullous lesions, have also rarely been reported.2 EED has a predilection for the extensor surfaces overlying joints,1 especially the hands, elbows and knees. Other sites, such as the face, trunk, palms and soles3 are less commonly affected. Histologically, EED is characterized as a leucocytoclastic vasculitis, with conspicuous dermal inflammatory polymorphic infiltrates. Development of EED has been associated with streptococcal, hepatitis and human immunodeficiency virus (HIV) infections.4 We report the case of a woman with a long history of unilateral erythematous nodules, initially diagnosed as fish-tank granulomata, but found to be EED histologically. Correspondence: Dr Charlotte Thomas, Dermatology Department, St George’s Hospital, Blackshaw Road, Tooting, London, SW17 0QT, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 21 October 2014
ª 2015 British Association of Dermatologists
Report A 27-year-old woman presented with a 4-month history of asymptomatic erythematous nodules overlying the proximal interphalangeal joints of the left middle and little fingers (Fig. 1), with the larger nodular lesion of the middle finger intermittently discharging a purulent exudate. There was no pruritus. These lesions had developed following minor trauma to the patient’s hand. She worked as an intensive care nurse. Her medical history included allergic rhinitis, but she was otherwise systemically well. Physical examination revealed erythematous nodules over the proximal interphalangeal joint of the left middle and third fingers. Clinically, the appearance was thought to be consistent with a fish-tank granuloma. However, there was no history of contact with fish-tank water. A punch biopsy confirmed the presence of neutrophilic abscesses surrounded by extensive granulomatous infiltrate, patchy lymphocytic aggregates and central necrosis (Fig. 2a). Despite the absence of organisms on slides after special stain for fungi and acid-fast bacilli, the histological appearance was consistent with the diagnosis of fish-tank granuloma, caused by Mycobacterium marinum infection. The patient was commenced on oral clarithromycin, which was continued for 9 months. Subsequent PCR from
Clinical and Experimental Dermatology (2015) 40, pp761–764
761
Unilateral erythema elevatum diutinum with IgA paraproteinaemia C. L. Thomas et al.
(a)
(a)
(b)
(b)
Figure 1 (a, b) Distribution of erythematous nodules overlying
the proximal interphalangeal joint of the middle finger of the left hand.
the biopsy sample was negative for nontuberculous mycobacteria, and there was little improvement with clarithromycin. Localized sporotrichosis was considered as a differential diagnosis, but despite 3 months of treatment with oral itraconazole, there was no improvement in the lesions. In light of the consistent negative microbiology and lack of clinical improvement with the prescribed treatment, the differential diagnosis was again revised. The nodules were suspected to be inflammatory in nature, possibly due to superficial granulomatous pyoderma or an atypical granuloma annulare, and a trial of intralesional triamcinolone resulted in some flattening of the primary lesion. Cutaneous leishmaniasis was not seriously considered as the patient had not travelled to an endemic area and gram stains were consistently negative. Because of the poor cosmesis, which was unacceptable due to her occupation in healthcare, the patient
762
Clinical and Experimental Dermatology (2015) 40, pp761–764
(c)
Figure 2 (a) Initial punch biopsy demonstrating neutrophilic
abscesses, surrounded by granulomatous inflammation. (b, c) Excision specimen, showing (b) nodules of spindle cells in a hyalinized stroma and focal central necrosis and (c) central necrosis, leucocytoclasis, and an accompanying infiltrate of neutrophils and eosinophils. Haematoxylin and eosin, original magnification (a) 9 40; (b) 9 440; (c) 9 4200.
ª 2015 British Association of Dermatologists
Unilateral erythema elevatum diutinum with IgA paraproteinaemia C. L. Thomas et al.
underwent excision of the nodule with a local flap. The excision specimen demonstrated hyperkeratosis and acanthosis of the epidermis and spindle cells in a hyalinized stroma, with numerous neutrophils, scattered eosinophils and leucocytoclasis with focal central necrosis (Fig. 2b,c). The appearance was consistent with a diagnosis of EED. Because the patient was still lesion-free and the lesion site had a good postoperative cosmetic appearance at the 1-year follow-up, systemic treatment was not started, although dapsone is the preferred management option in the event of a recurrence or development of new lesions. Blood testing at diagnosis had demonstrated no evidence of infections such as streptococcus was negative, HIV or hepatitis, and autoimmune screen was negative but serum protein electrophoresis did reveal a monoclonal gammopathy, and immunofixation confirmed depressed IgM levels and an IgA kappa monoclonal protein band. Following a negative skeletal survey and detection of urinary Bence Jones proteins, the patient was diagnosed with monoclonal gammopathy of uncertain significance (MGUS), and remains under haematological follow-up. This case of unilateral EED was initially diagnosed as M. marinum infection. The clinical presentation of EED is morphologically varied, and histological analysis is therefore an essential correlate for diagnosis. Owing to the intense neutrophilic infiltrate seen on biopsies from patients with EED, it is not unusual for the histological differential diagnoses to contain infective processes; however, despite PCR and extended culture in our case, microbiological results were consistently negative. The appearance of disease at sites of trauma and particularly on the extensor surfaces of proximal interphalangeal joints is typical; however, EED is characteristically described as symmetrical and bilateral. The unilateral presentation in our patient, with two isolated lesions on the left hand, was therefore striking. Unilateral disease appears to be a very rare presentation of this already uncommon condition, but has previously been reported by Kharkar et al.5 Our patient’s localized disease was treated with excision before confirmation of the diagnosis. EED is commonly treated medically with dapsone with a good outcome,6 although excision has also been used effectively.7 For the localized disease in this case, excision appears to have been a successful treatment. This case highlights an example of one of the many systemic associations with EED: IgA kappa paraproteinaemia. EED has been shown to be linked with elevated IgA levels in addition to IgA paraprotein-
ª 2015 British Association of Dermatologists
aemia and IgA myeloma.8 Yiannias et al. reported that 4 of the 13 patients in their case series had coexisting IgA paraprotein, and the fifth had myeloma. The mechanism of association between EED and IgA paraproteinaemia in preference to the other immunoglobulin subtypes is unknown. Other haematological associations include myelodysplasia.8 Given the small number of reported cases of EED, some authors have suggested that the presence of EED and these systemic diseases represents no more than comorbidity. However, it remains clear that thorough investigation for the presence of a potentially fatal systemic disease is essential after EED diagnosis. Moreover, as EED often precedes the haematological diagnosis by 5–10 years,8 there is a need for ongoing symptom and blood monitoring long after the diagnosis of EED is made. The rate of progression from MGUS to myeloma is 1%/year, and the cumulative risk is 10% at 10 years,9 thus follow-up of patients diagnosed with MGUS is essential. The IgA MGUS subtype itself is also a risk factor for transformation to myeloma,9 therefore such patients should be reviewed by the haematology department every 3–4 months for the first year after diagnosis, reducing to every 6–12 months if there are no clinical or laboratory features of concern.10
Learning points The typical distribution of EED is symmetrical
and bilateral, overlying the extensor surfaces, but unilateral presentations are possible. Surgical excision is an appropriate management option for localized disease. Once a diagnosis of EED has been made, the patient must be investigated thoroughly for underlying systemic diseases including MGUS, multiple myeloma and myelodysplasia.
References 1 Gibson LE, El-Azhary RA. Erythema elevatum diutinum. Clin Dermatol 2000; 18: 295–9. 2 Agusti-Mejias A, Messeguer-Badia F, Rodriguez M et al. Erythema elevatum diutinum mimicking disease. Int J Dermatol 2011; 50: 1126–8. 3 Barzegar M, Davatchi CC, Akhyani M et al. An atypical presentation of erythema elevatum diutinum involving palms and soles. Int J Dermatol 2009; 48: 73–5.
Clinical and Experimental Dermatology (2015) 40, pp761–764
763
Unilateral erythema elevatum diutinum with IgA paraproteinaemia C. L. Thomas et al.
4 Muratori S, Carrera C, Gorani A et al. Erythema elevatum diutinum and HIV infection: a report of five cases. Br J Dermatol 1999; 141: 335–8. 5 Kharkar V, Gutte R, Mahajan S, Khopkar U. Isolated unilateral erythema elevatum diutinum: a case report. EDOJ 2011; 7: 1–6. Available at http://www.edoj.org.eg/ vol007/0702/008/paper.pdf (accessed 7 July 2014). 6 Fort LS, Rodman OG. Erythema elevatum diutinum. Response to dapsone. Arch Dermatol 1977; 113: 819–22. 7 Rinard JR, Mahabir RC, Greene JF et al. Successful surgical treatment of advanced erythema elevatum diutinum. Can J Plast Surg 2010; 18: 28–30.
764
Clinical and Experimental Dermatology (2015) 40, pp761–764
8 Yiannias JA, El-Azhary RA, Gibson LE. Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients. J Am Acad Dermatol 1992; 26: 38–44. 9 Kyle RA, Therneau TM, Rajkumar SV et al. A long- term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 2002; 346: 564–9. 10 Bird J, Behrens J, Westin J et al. Guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol 2009; 147: 22–42.
ª 2015 British Association of Dermatologists
Clinical dermatology • Concise report
Clinical and Experimental Dermatology
A case of mistaken identity: unilateral erythema elevatum diutinum associated with IgA paraproteinaemia C. L. Thomas, L. Ffolkes and V. Akhras Department of Dermatology, St George’s Hospital, London, UK doi:10.1111/ced.12622
Summary
We report the case of a 27-year-old woman presenting with unilateral painless nodules of the left hand following trauma. Initially diagnosed as nontuberculous mycobacterium infection and treated with prolonged courses of antibiotics with little improvement, the condition was subsequently diagnosed histologically as erythema elevatum diutinum (EED). The lesion was treated with surgical excision, and the patient remained lesion-free at the 1-year follow-up. Although the lesion was otherwise asymptomatic, further investigation demonstrated an underlying IgA paraproteinaemia. This case should alert physicians to consider the diagnosis of EED in a unilateral presentation, and highlights the importance of investigation for underlying associated haematological disease.
Erythema elevatum diutinum (EED) is a rare chronic form of cutaenous vasculitis, which falls within the subgroup of neutrophilic dermatoses (also including Sweet syndrome and pyoderma gangrenosum). Clinically, the presentation of EED is diverse. It is characterized by the presence of plaques, papules or nodules, which may be erythematous, brown or violaceous in colour.1 Atypical presentations, such as vesiculobullous lesions, have also rarely been reported.2 EED has a predilection for the extensor surfaces overlying joints,1 especially the hands, elbows and knees. Other sites, such as the face, trunk, palms and soles3 are less commonly affected. Histologically, EED is characterized as a leucocytoclastic vasculitis, with conspicuous dermal inflammatory polymorphic infiltrates. Development of EED has been associated with streptococcal, hepatitis and human immunodeficiency virus (HIV) infections.4 We report the case of a woman with a long history of unilateral erythematous nodules, initially diagnosed as fish-tank granulomata, but found to be EED histologically. Correspondence: Dr Charlotte Thomas, Dermatology Department, St George’s Hospital, Blackshaw Road, Tooting, London, SW17 0QT, UK E-mail: [email protected] Conflict of interest: the authors declare that they have no conflicts of interest. Accepted for publication 21 October 2014
ª 2015 British Association of Dermatologists
Report A 27-year-old woman presented with a 4-month history of asymptomatic erythematous nodules overlying the proximal interphalangeal joints of the left middle and little fingers (Fig. 1), with the larger nodular lesion of the middle finger intermittently discharging a purulent exudate. There was no pruritus. These lesions had developed following minor trauma to the patient’s hand. She worked as an intensive care nurse. Her medical history included allergic rhinitis, but she was otherwise systemically well. Physical examination revealed erythematous nodules over the proximal interphalangeal joint of the left middle and third fingers. Clinically, the appearance was thought to be consistent with a fish-tank granuloma. However, there was no history of contact with fish-tank water. A punch biopsy confirmed the presence of neutrophilic abscesses surrounded by extensive granulomatous infiltrate, patchy lymphocytic aggregates and central necrosis (Fig. 2a). Despite the absence of organisms on slides after special stain for fungi and acid-fast bacilli, the histological appearance was consistent with the diagnosis of fish-tank granuloma, caused by Mycobacterium marinum infection. The patient was commenced on oral clarithromycin, which was continued for 9 months. Subsequent PCR from
Clinical and Experimental Dermatology (2015) 40, pp761–764
761
Unilateral erythema elevatum diutinum with IgA paraproteinaemia C. L. Thomas et al.
(a)
(a)
(b)
(b)
Figure 1 (a, b) Distribution of erythematous nodules overlying
the proximal interphalangeal joint of the middle finger of the left hand.
the biopsy sample was negative for nontuberculous mycobacteria, and there was little improvement with clarithromycin. Localized sporotrichosis was considered as a differential diagnosis, but despite 3 months of treatment with oral itraconazole, there was no improvement in the lesions. In light of the consistent negative microbiology and lack of clinical improvement with the prescribed treatment, the differential diagnosis was again revised. The nodules were suspected to be inflammatory in nature, possibly due to superficial granulomatous pyoderma or an atypical granuloma annulare, and a trial of intralesional triamcinolone resulted in some flattening of the primary lesion. Cutaneous leishmaniasis was not seriously considered as the patient had not travelled to an endemic area and gram stains were consistently negative. Because of the poor cosmesis, which was unacceptable due to her occupation in healthcare, the patient
762
Clinical and Experimental Dermatology (2015) 40, pp761–764
(c)
Figure 2 (a) Initial punch biopsy demonstrating neutrophilic
abscesses, surrounded by granulomatous inflammation. (b, c) Excision specimen, showing (b) nodules of spindle cells in a hyalinized stroma and focal central necrosis and (c) central necrosis, leucocytoclasis, and an accompanying infiltrate of neutrophils and eosinophils. Haematoxylin and eosin, original magnification (a) 9 40; (b) 9 440; (c) 9 4200.
ª 2015 British Association of Dermatologists
Unilateral erythema elevatum diutinum with IgA paraproteinaemia C. L. Thomas et al.
underwent excision of the nodule with a local flap. The excision specimen demonstrated hyperkeratosis and acanthosis of the epidermis and spindle cells in a hyalinized stroma, with numerous neutrophils, scattered eosinophils and leucocytoclasis with focal central necrosis (Fig. 2b,c). The appearance was consistent with a diagnosis of EED. Because the patient was still lesion-free and the lesion site had a good postoperative cosmetic appearance at the 1-year follow-up, systemic treatment was not started, although dapsone is the preferred management option in the event of a recurrence or development of new lesions. Blood testing at diagnosis had demonstrated no evidence of infections such as streptococcus was negative, HIV or hepatitis, and autoimmune screen was negative but serum protein electrophoresis did reveal a monoclonal gammopathy, and immunofixation confirmed depressed IgM levels and an IgA kappa monoclonal protein band. Following a negative skeletal survey and detection of urinary Bence Jones proteins, the patient was diagnosed with monoclonal gammopathy of uncertain significance (MGUS), and remains under haematological follow-up. This case of unilateral EED was initially diagnosed as M. marinum infection. The clinical presentation of EED is morphologically varied, and histological analysis is therefore an essential correlate for diagnosis. Owing to the intense neutrophilic infiltrate seen on biopsies from patients with EED, it is not unusual for the histological differential diagnoses to contain infective processes; however, despite PCR and extended culture in our case, microbiological results were consistently negative. The appearance of disease at sites of trauma and particularly on the extensor surfaces of proximal interphalangeal joints is typical; however, EED is characteristically described as symmetrical and bilateral. The unilateral presentation in our patient, with two isolated lesions on the left hand, was therefore striking. Unilateral disease appears to be a very rare presentation of this already uncommon condition, but has previously been reported by Kharkar et al.5 Our patient’s localized disease was treated with excision before confirmation of the diagnosis. EED is commonly treated medically with dapsone with a good outcome,6 although excision has also been used effectively.7 For the localized disease in this case, excision appears to have been a successful treatment. This case highlights an example of one of the many systemic associations with EED: IgA kappa paraproteinaemia. EED has been shown to be linked with elevated IgA levels in addition to IgA paraprotein-
ª 2015 British Association of Dermatologists
aemia and IgA myeloma.8 Yiannias et al. reported that 4 of the 13 patients in their case series had coexisting IgA paraprotein, and the fifth had myeloma. The mechanism of association between EED and IgA paraproteinaemia in preference to the other immunoglobulin subtypes is unknown. Other haematological associations include myelodysplasia.8 Given the small number of reported cases of EED, some authors have suggested that the presence of EED and these systemic diseases represents no more than comorbidity. However, it remains clear that thorough investigation for the presence of a potentially fatal systemic disease is essential after EED diagnosis. Moreover, as EED often precedes the haematological diagnosis by 5–10 years,8 there is a need for ongoing symptom and blood monitoring long after the diagnosis of EED is made. The rate of progression from MGUS to myeloma is 1%/year, and the cumulative risk is 10% at 10 years,9 thus follow-up of patients diagnosed with MGUS is essential. The IgA MGUS subtype itself is also a risk factor for transformation to myeloma,9 therefore such patients should be reviewed by the haematology department every 3–4 months for the first year after diagnosis, reducing to every 6–12 months if there are no clinical or laboratory features of concern.10
Learning points The typical distribution of EED is symmetrical
and bilateral, overlying the extensor surfaces, but unilateral presentations are possible. Surgical excision is an appropriate management option for localized disease. Once a diagnosis of EED has been made, the patient must be investigated thoroughly for underlying systemic diseases including MGUS, multiple myeloma and myelodysplasia.
References 1 Gibson LE, El-Azhary RA. Erythema elevatum diutinum. Clin Dermatol 2000; 18: 295–9. 2 Agusti-Mejias A, Messeguer-Badia F, Rodriguez M et al. Erythema elevatum diutinum mimicking disease. Int J Dermatol 2011; 50: 1126–8. 3 Barzegar M, Davatchi CC, Akhyani M et al. An atypical presentation of erythema elevatum diutinum involving palms and soles. Int J Dermatol 2009; 48: 73–5.
Clinical and Experimental Dermatology (2015) 40, pp761–764
763
Unilateral erythema elevatum diutinum with IgA paraproteinaemia C. L. Thomas et al.
4 Muratori S, Carrera C, Gorani A et al. Erythema elevatum diutinum and HIV infection: a report of five cases. Br J Dermatol 1999; 141: 335–8. 5 Kharkar V, Gutte R, Mahajan S, Khopkar U. Isolated unilateral erythema elevatum diutinum: a case report. EDOJ 2011; 7: 1–6. Available at http://www.edoj.org.eg/ vol007/0702/008/paper.pdf (accessed 7 July 2014). 6 Fort LS, Rodman OG. Erythema elevatum diutinum. Response to dapsone. Arch Dermatol 1977; 113: 819–22. 7 Rinard JR, Mahabir RC, Greene JF et al. Successful surgical treatment of advanced erythema elevatum diutinum. Can J Plast Surg 2010; 18: 28–30.
764
Clinical and Experimental Dermatology (2015) 40, pp761–764
8 Yiannias JA, El-Azhary RA, Gibson LE. Erythema elevatum diutinum: a clinical and histopathologic study of 13 patients. J Am Acad Dermatol 1992; 26: 38–44. 9 Kyle RA, Therneau TM, Rajkumar SV et al. A long- term study of prognosis in monoclonal gammopathy of undetermined significance. N Engl J Med 2002; 346: 564–9. 10 Bird J, Behrens J, Westin J et al. Guidelines for the investigation of newly detected M-proteins and the management of monoclonal gammopathy of undetermined significance (MGUS). Br J Haematol 2009; 147: 22–42.
ª 2015 British Association of Dermatologists
