Journal Information
Vol. 104. Issue 3.
Pages 257-259 (April 2013)
Vol. 104. Issue 3.
Pages 257-259 (April 2013)
Case and Research Letters
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Mixed Panniculitis Secondary to Interferon Beta-1a Therapy in a Woman With Multiple Sclerosis
Paniculitis mixta secundaria al uso de interferón β 1A en una paciente con esclerosis múltiple
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L. Cuestaa,
Corresponding author
lcuestamontero@hotmail.com

Corresponding author.
, M. Moragóna, M. Pérez-Crespoa, J. Onrubiab, M. Garcíaa
a Servicio de Dermatología, Hospital Clínico Universitario San Juan, Alicante, Spain
b Servicio de Anatomía Patológica, Hospital Clínico Universitario San Juan, Alicante, Spain
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Table 1. Patients Described in the Literature Who Developed Panniculitis After Interferon Administration.
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To the Editor:

Interferon beta was approved in Spain in 1995 for the treatment of progressive multiple sclerosis. There are 2 main types, interferon beta-1a and 1b, both of which are sold in a variety of formulations, resulting in a range of responses to the same molecule. Local skin reactions are a common adverse effect, and are usually self-limiting. By contrast, panniculitis and lipoatrophy are very rare, and may necessitate discontinuation of treatment.

We describe the case of a 43-year-old woman who was diagnosed in 2005 with multiple sclerosis, for which she received several disease-modifying treatments. In October 2009, she began treatment with interferon beta-1a (Rebif 44), which was self-administered subcutaneously 3 times a week, with a favorable response. After 18 months of treatment, induration was observed at the injection sites, on the back of the thighs, and on the outer arms. A few weeks later, ulcerated lesions appeared on the front of the thighs and progressively increased in size. The patient reported that the plaques caused severe pain, which made moving and walking difficult. She reported no fever or systemic upset and her neurological status remained unchanged.

Examination revealed 2 ulcers on the front of the thighs of 1cm diameter. The borders of the ulcers had a scarlike appearance and beneath the ulcers were cavities of about 4cm in diameter. An indurated plaque of about 15cm in diameter, with a slightly erythematous surface, surrounded the ulcer and was intensely painful to touch (Fig. 1). These indurated plaques were also present on the external aspect of both arms, although no ulcers were observed.

Figure 1.

Indurated erythematous plaques with ulcerated centers on the front of both thighs.

(0.12MB).

Tissue culture of the ulcers and an incisional biopsy of a plaque from 1 of the thighs were negative. Histopathology revealed a preserved epidermis, sclerosis of the middle and deep dermis, and subcutaneous tissue involvement. At higher magnification we detected an infiltrate that primarily affected the lobule, although septal thickening was also observed (Fig. 2a); this infiltrate was composed mainly of neutrophils and lymphocytes (Fig. 2b). No vasculitis or necrosis was observed. Based on these observations, the patient was diagnosed with mixed panniculitis secondary to interferon beta-1a therapy. Upon consultation with her neurologist, it was decided to discontinue interferon beta-1a treatment, mainly due to functional impairment.

Figure 2.

a, An infiltrate affecting the lobule and to a lesser extent, the septum. Septal thickening is also observed. Hematoxylin-eosin, original magnification ×40. b, Mixed infiltrate composed mainly of lymphocytes with some neutrophils. Hematoxylin-eosin, original magnification ×200.

(0.56MB).

Interferon beta-1a was approved for the treatment of progressive multiple sclerosis in Spain in 1995. Its administration decreases the relapse rate by 30% and the appearance of new lesions on magnetic resonance imaging by 66%. Local skin manifestations such as erythema and pain are well-described frequent adverse effects; they occur in 63% to 85% of patients1 but are usually self-limiting and do not require discontinuation of treatment. However, treatment may need to be discontinued in cases of other more serious reactions such as ulcerations, necrosis,2 sclerosis, and induration at the injection site. Other adverse effects such as sarcoid granulomas, lipoatrofia,3 lupus-like lesions,4 and septal or lobular panniculitis5 are considered very rare. Table 1 summarizes the cases of panniculitis secondary to interferon treatment described to date. Some authors have suggested that this form of panniculitis may be caused by the vascular toxicity of interferon beta.

Table 1.

Patients Described in the Literature Who Developed Panniculitis After Interferon Administration.

  Age, Sex  Location  Onset of Symptoms  Clinical Symptoms  Pathological Findings 
Nakamura et al.,52008  43, female  Buttocks  5 y  Erythema, induration, and pain  Perivascular dermatitis and lobular and septal panniculitis with lymphocytic infiltrate 
Ziegler et al.,61998  41, female  Legs  8 wk  Erythema, induration, and pain  Perivascular infiltrate and lobular panniculitis with lymphocytic infiltrate 
Heinzerling et al.,72002  44, female  Arms, legs and abdomen  4 y  Painful induration  Septal panniculitis with predominantly lymphocytic infiltrate 
O'Sullivan et al.,82006  37, male  Left leg  2 y, 3 mo  Erythema and pain  Septal panniculitis with inflammatory infiltrate 
Ball et al.,92009  46, female  Not recorded  1 y, 10 mo  Pain and induration  Lobular panniculitis with neutrophilic infiltrate 
Ball et al.,92009  45, female  Not recorded  6 y, 1 mo  Cellulitis  Lipomembranous panniculitis 
Poulin et al.,102009  43, female  Abdomen  9 y  Erythema, pain, and fever  Septal panniculitis with predominantly lymphocytic infiltrate 
Present case  43, female  Legs  19 mo  Pain, erythema, induration, and functional impairment  Lobular and septal panniculitis with mixed inflammatory infiltrate (lymphocytes and neutrophils) 

In 2009, Ball and coworkers9 reported that interferon beta-induced panniculitis can mimic pancreatic panniculitis; differential diagnosis in such cases may be facilitated by lipase and amylase tests.

Two theories have been proposed regarding the pathophysiology of panniculitis secondary to interferon beta treatment. The first proposes that the stress associated with self-injection plays a key role in triggering this condition. The second theory attributes greater importance to the immunological effects of interferon beta. According to the latter theory, the resulting symptoms reflect activation of the immune system and may be an indication of treatment effectiveness.9

The management of patients with panniculitis secondary to interferon beta treatment remains unsatisfactory. It is essential that patients are shown how to correctly self-administer the injection, which should be subcutaneous and never intradermal, and to rotate the injection sites daily. Application of these measures leads to improvements in the majority of lesions,5 although in some cases suspension of interferon beta treatment may be necessary, a decision that should be made in collaboration with the other specialists treating the patient.

References
[1]
A.R. Gaines, F. Varricchio.
Interferon beta-1b injection site reactions and necroses.
Mult Scler, 4 (1998), pp. 70
[2]
G. Aguilar, C. Serrano, M. Carmona, J. Linares, S. Serrano.
Necrosis cutánea por interferón alfa en paciente con melanoma.
Actas Dermosifiliogr, 97 (2006), pp. 539-542
[3]
A.G. Beiske, K.M. Myhr.
Lipoatrophy: a non-reversible complication of subcutaneous interferon-beta 1a treatment of multiple sclerosis.
J Neurol, 253 (2006), pp. 377-378
[4]
I. Arrue, A. Saiz, P.L. Ortiz-Romero, J.L. Rodríguez-Peralto.
Lupus-like reaction to interferon at the injection site: report of five cases.
J Cutan Pathol, 34 (2007), pp. 18-21
[5]
Y. Nakamura, Y. Kawachi, J. Furuta, F. Otsuka.
Severe local skin reactions to interferon beta-1b in multiple sclerosis-improvement by deep subcutaneous injection.
Eur J Dermatol, 18 (2008), pp. 579-582
[6]
V.R. Ziegler, B. Kranke, P. Soyer, W. Aberer.
Extensive cutaneous-subcutaneous infiltration as a side-effect of interferon beta injection.
Hautarzt, 49 (1998), pp. 310
[7]
L. Heinzerling, R. Dummer, G. Burg, P. Schmid-Grendelmeier.
Panniculitis after subcutaneous injection of interferon beta in a multiple sclerosis patient.
Eur J Dermatol, 12 (2002), pp. 194-197
[8]
S.S. O'Sullivan, E.M. Cronin, B.J. Sweeney, J.F. Bourke, J. Fitzgibbon.
Panniculitis and lipoatrophy after subcutaneous injection of interferon beta-1b in a patient with multiple sclerosis.
J Neurol Neurosurg Psychiatry, 77 (2006), pp. 1382-1383
[9]
N.J. Ball, B.J. Cowan, S.A. Hashimoto.
Lobular panniculitis at the site of subcutaneous interferon beta injections for the treatment of multiple sclerosis can histologically mimic pancreatic panniculitis. A study of 12 cases.
J Cutan Pathol, 36 (2009), pp. 331-337
[10]
F. Poulin, P. Rico, J. Côté, L.R. Bégin.
Interferon beta-induced panniculitis mimicking acute appendicitis.
Arch Dermatol, 145 (2009), pp. 916-917

Please cite this article as: Cuesta L, et al. Paniculitis mixta secundaria al uso de interferón β 1A en una paciente con esclerosis múltiple. Actas Dermosifiliogr. 2013;104:257–9.

Copyright © 2012. Elsevier España, S.L. and AEDV
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