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Interferon Beta–Induced Panniculitis Mimicking Acute Appendicitis FREE

Philippe Rico, MD
[+] Author Affiliations

Author Affiliations: Department of Internal Medicine (Drs Poulin and Rico), Divisions of Dermatology (Dr Côté) and Anatomic Pathology (Dr Bégin), Hôpital du Sacré-Cœur de Montréal and University of Montréal, Montréal, Québec, Canada.


Arch Dermatol. 2009;145(8):916-917. doi:10.1001/archdermatol.2009.106.
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Published online

Background  As immunomodulatory therapies such as recombinant human interferon beta gain clinical applicability, patients are likely to experience some of their numerous cutaneous adverse effects at injection sites. We describe a case of interferon beta–induced septal panniculitis.

Observations  A 43-year-old woman with multiple sclerosis treated with subcutaneous interferon beta presented with right lower abdominal quadrant pain, fever, and an indurated McBurney point. An abdominal computed tomographic scan showed an inflammatory subcutaneous fat infiltration reaching the surface of the right lateral rectus muscle. The patient was brought to the operating room, where a laparoscopic appendectomy was performed. She returned a week later unimproved. The infiltration near a site of subcutaneous injection progressed with areas of liquefaction. Histologic examination of a deep cutaneous biopsy specimen revealed a septal panniculitis without vasculitis.

Conclusions  Panniculitides encompass various clinical syndromes characterized by inflammation of the fibrous septae, fatty lobules, or both components of the subcutaneous tissue. Interferon beta-1b should be considered among the list of putative agents.

Figures in this Article

Since the discovery in 1957 of interferons, enthusiasm about their efficacy in the treatment of chronic debilitating diseases such as multiple sclerosis (MS) has endured. Multiple sclerosis is a complex demyelinating disease of the central nervous system. Dysregulation of cellular and humoral immune mechanisms and molecular defects in interferon signaling pathways support the use of immunomodulatory therapies such as recombinant human interferon beta. Over a decade of clinical trials led to its approval and also unveiled a spectrum of cutaneous adverse effects at injection sites.1

We describe a case of recombinant human interferon beta-1b–induced septal panniculitis in a 43-year-old woman with a 10-year history of MS. Treatment with subcutaneous injection of recombinant human interferon beta-1b was initiated in 1997. Injection sites were rotated between the left and right lower abdomen and lower limbs.

In 2006, the patient experienced right lower quadrant abdominal (RLQ) pain with fever. An abdominal examination revealed a tender and indurated McBurney point. Findings from routine blood tests showed mild leukocytosis and results from 2 blood cultures were within reference range. An abdominal computed tomographic (CT) scan demonstrated a subcutaneous fat infiltration reaching the right lateral rectus muscle (Figure 1). Even though the appendix appeared to be normal, the clinical diagnosis of appendicitis was maintained, and a laparoscopic appendectomy was performed. Pathological examination findings revealed only a small appendiceal fecalith.

Place holder to copy figure label and caption
Figure 1.

Abdominal computed tomographic scan shows area of subcutaneous fat infiltration reaching the surface of right lateral rectus muscle (arrow). R indicates right; L, left; and P, posterior.

Graphic Jump Location

The patient returned 1 week later, and her condition was unimproved. A 10 × 8-cm2 induration of her RLQ abdominal wall was noted near a common site of interferon injection. Postoperative deep-tissue infection was suspected, and treatment with empirical broad-spectrum antibiotics was started without noticeable improvement. An abdominal CT scan revealed progression of subcutaneous infiltration with areas of liquefaction. A diagnosis of panniculitis secondary to interferon beta-1b injection was considered. Histologic examination of a deep cutaneous biopsy specimen revealed a septal panniculitis, including a mixed cell infiltrate of lymphocytes, plasma cells, and histiocytes without evidence of vasculitis or intravascular thrombosis (Figure 2).

Place holder to copy figure label and caption
Figure 2.

Interface between subcutaneous septa (left two-thirds) and fat (right one-third) showing marked widening of the septa resulting from edema and a cellular infiltrate, characteristic of a pattern of septal panniculitis (hematoxylin-eosin, original magnification ×100).

Graphic Jump Location

Antibiotic therapy was discontinued, and treatment with a nonsteroidal anti-inflammatory drug was begun. At the 3-week follow-up, the patient elected to continue her interferon beta-1b injections, but avoiding her abdomen, and she experienced a slow resolution of her panniculitis.

We report herein a case of interferon beta-1b–induced septal panniculitis of the abdominal wall mimicking appendicitis. Recent avoidance of the patient's lower limbs as injection sites for personal reasons may explain the late appearance of panniculitis since interferon treatment initiation. Panniculitides encompass various clinical syndromes characterized by inflammation of the fibrous septae, fatty lobules, or both components of the subcutaneous tissue.

Septal panniculitis is an unusual cutaneous adverse reaction related to immunomodulatory therapy of MS.2,3 Cutaneous reactions at injection sites are frequently described (in ≤44% of patients), ranging from benign painful erythema to skin necrosis. Mechanisms of pathogenesis are not fully understood. Immunologically mediated necrotizing vasculitis and platelet-dependent thrombosis in the dermis may play a role. Multiple sclerosis per se or its immunomodulatory treatment seems to trigger clotting abnormalities, as shown by a consistent activation of platelets in these patients.4 More recently, Buttmann et al5 demonstrated the direct induction of local chemokine expression and the associated immune cell extravasation caused by interferon beta in human skin biopsy specimens.

It remains unclear how to handle interferon beta-1b therapy. Switching from a subcutaneous to an intramuscular route of administration, diluting the preparation, and changing to an alternative interferon have all been advocated. We suggest a trial of an enteral nonsteroidal anti-inflammatory drug. Clinicians should consider interferon beta-1b among the list of putative agents that induce septal panniculitis.

Correspondence: Frédéric Poulin, MD, FRCPC, Hôpital du Sacré-Cœur de Montréal, Department of Internal Medicine, 5400 Gouin Blvd W, Montréal, Québec, Canada H4J 1C5 (f.poulin@umontreal.ca).

Accepted for Publication: November 11, 2008.

Author Contributions: All authors had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Poulin and Rico. Acquisition of data: Poulin. Analysis and interpretation of data: Poulin, Côté, and Bégin. Drafting of the manuscript: Poulin. Critical revision of the manuscript for important intellectual content: Rico, Côté, and Bégin. Administrative, technical, and material support: Poulin and Bégin. Study supervision: Poulin, Rico, and Côté.

Financial Disclosure: None reported.

Walther  EUHohlfeld  R Multiple sclerosis: side effects of interferon beta therapy and their management. Neurology 1999;53 (8) 1622- 1627
PubMed
Heinzerling  LDummer  RBurg  GSchmid-Grendelmeier  P Panniculitis after subcutaneous injection of interferon beta in a multiple sclerosis patient. Eur J Dermatol 2002;12 (2) 194- 197
PubMed
O'Sullivan  SSCronin  EMSweeney  BJBourke  JFFitzgibbon  J Panniculitis and lipoatrophy after subcutaneous injection of interferon beta-1b in a patient with multiple sclerosis. J Neurol Neurosurg Psychiatry 2006;77 (12) 1382- 1383
PubMed
Elgart  GWSheremata  WAhn  YS Cutaneous reactions to recombinant human interferon beta-1b: the clinical and histologic spectrum. J Am Acad Dermatol 1997;37 (4) 553- 558
PubMed
Buttmann  MGoebeler  MToksoy  A  et al.  Subcutaneous interferon-beta injections in patients with multiple sclerosis initiate inflammatory skin reactions by local chemokine induction. J Neuroimmunol 2005;168 (1-2) 175- 182
PubMed

Figures

Place holder to copy figure label and caption
Figure 1.

Abdominal computed tomographic scan shows area of subcutaneous fat infiltration reaching the surface of right lateral rectus muscle (arrow). R indicates right; L, left; and P, posterior.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.

Interface between subcutaneous septa (left two-thirds) and fat (right one-third) showing marked widening of the septa resulting from edema and a cellular infiltrate, characteristic of a pattern of septal panniculitis (hematoxylin-eosin, original magnification ×100).

Graphic Jump Location

Tables

References

Walther  EUHohlfeld  R Multiple sclerosis: side effects of interferon beta therapy and their management. Neurology 1999;53 (8) 1622- 1627
PubMed
Heinzerling  LDummer  RBurg  GSchmid-Grendelmeier  P Panniculitis after subcutaneous injection of interferon beta in a multiple sclerosis patient. Eur J Dermatol 2002;12 (2) 194- 197
PubMed
O'Sullivan  SSCronin  EMSweeney  BJBourke  JFFitzgibbon  J Panniculitis and lipoatrophy after subcutaneous injection of interferon beta-1b in a patient with multiple sclerosis. J Neurol Neurosurg Psychiatry 2006;77 (12) 1382- 1383
PubMed
Elgart  GWSheremata  WAhn  YS Cutaneous reactions to recombinant human interferon beta-1b: the clinical and histologic spectrum. J Am Acad Dermatol 1997;37 (4) 553- 558
PubMed
Buttmann  MGoebeler  MToksoy  A  et al.  Subcutaneous interferon-beta injections in patients with multiple sclerosis initiate inflammatory skin reactions by local chemokine induction. J Neuroimmunol 2005;168 (1-2) 175- 182
PubMed

Correspondence

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