Isolated Gastrocnemius Myositis Related to Crohn's Disease

The prevalence of extraintestinal manifestations in inflammatory bowel disease patients ranges from 21% to 40%.^1–3 The most commonly involved organ systems are the musculoskeletal, mucocutaneous, ophthalmologic, and hepatobiliary. In several case series, it has been postulated that there may be a greater prevalence of extraintestinal manifestations in Crohn's disease patients.⁴ Gastrocnemius myalgia syndrome is a rare extraintestinal manifestation that has been reported in 8 other published cases.^5–13 This case report may be the first presentation of this atypical extraintestinal manifestation of Crohn's disease to be reported in the United States. The patient's bilateral calf myalgia was distinctive and recurrent and required a novel therapeutic approach.

Case Report

A 15-year-old white male with a 5-year history of ileocolonic Crohn's disease presented with acute onset of bilateral localized calf tenderness and Achilles pain for 1.5 weeks. The pain was described as burning, with a feeling of tightness localized to the gastrocnemius muscle, causing difficulty in ambulation. The patient's pediatric gastroenterologist prescribed methylprednisolone, which resolved the symptoms. His bilateral calf muscle pain returned after 1 month. Methylprednisolone was prescribed once again but produced only a transient response, with a return of symptoms over the subsequent 2 days. The patient reported that the calf muscle discomfort was not prompted by any trauma, and he did not experience any abdominal or systemic symptoms. The patient's previous 3 hospital admissions, in 2001, 2003, and 2004, were related to his Crohn's disease. No other extraintestinal manifestations were reported.

Physical examination revealed significant tenderness of both calves and achilles tendons. No swelling, erythema, or indurated nodules were observed around the gastrocnemius muscle. The neurologic examination depicted a motor strength of 5 out of 5 throughout, with an intact sensory examination. His examination was otherwise unremarkable, with normal vital signs. The only medication he was taking at the time of presentation was controlled-release mesalamine (Pentasa, Shire) 100 mg 3 times daily. His family history was deemed to be non-contributory, and he denied any tobacco or alcohol use.

Laboratory values revealed a white blood cell count of 11.5 × 10³/μL with elevated neutrophils (77%), a hemoglobin level of 12.4 g/dL with a mean corpuscular volume of 71 fL, a mildly elevated erythrocyte sedimentation rate of 26 mm/hr, and a serum globulin level of 3.2 g/dL. The patient's basic metabolic panel was within normal limits except for a glucose level of 104 mg/dL. His creatine kinase was 86 U/L (normal, 22–198 U/L) and amylase was 91 U/L (normal, 23–85 U/L), and his liver function tests and urinalysis were all within normal limits. The patient's antineutrophil cytoplasmic antibodies (c-ANCA) were negative (<1:20), as were his atypical perinuclear antineutrophilic cytoplasmic antibodies (<1:20) and his antimyeloperoxidase antibody (titer 1:2). An antinuclear antibody direct test measured 30 units (negative <100), and aldolase measured 5.9 U/L (normal, 1.2–7.6 U/L).

An ultrasound venous Doppler of the bilateral lower extremities revealed no deep venous thrombosis. Magnetic resonance imaging showed diffuse inflammation of the gastrocnemius and soleus muscle groups with contrast enhancement that was consistent with a polymyositis. A biopsy of the left gastrocnemius muscle showed a moderate epimysial mixed chronic inflammatory infiltrate. Scant perivascular chronic inflammation was focally present around small capillaries within muscle fascicles (Figures 1 and 2). Vasculitis or degenerating/regenerating muscle fibers were not reported.

Figure 1.

Hematoxylin and eosin stain revealing a moderate, predominantly epimysial, mixed, chronic inflammatory infiltrate.

Figure 2.

Hematoxylin and eosin stain revealing a mild perivascular lymphocytic infiltrate but no vasculitis.

The patient was started on 40 mg daily of prednisone, which was tapered after reports of pain resolution 4 days later. The dose was further tapered to 10 mg daily (day 17) and resulted in pain located in the gastrocnemius muscle along with difficulty in ambulation. The patient continued to take 10 mg daily of prednisone. After reducing the dose to 2.5 mg, he experienced a flare of intestinal Crohn's disease that required hospitalization and treatment with methylprednisolone (Solu Medrol, Pharmacia and Upjohn). The patient was then started on 15–20 mg of methotrexate orally every week with 1 mg daily of folic acid. One year later, the patient reported no recurrence of bilateral calf myalgia on this regimen.

Discussion

The cases of calf-limited myalgia reported in the literature all responded to prednisolone, except for 1 case reported by Dioszeghy and associates (Table 1).^6–12 Case reports of a 21-year-old female and a 26-year-old female described the use of a combination treatment regimen of prednisolone plus azathioprine or cyclophosphamide. Our patient initially responded to prednisolone, but the symptoms of calf myalgia returned. He required methotrexate 15 –20 mg weekly for complete resolution of the pain.

Table 1.

Reports in the Literature of Gastrocnemius Myositis in Patients With Crohn's Disease

Study	Country	Gender	Age (years)	Muscle biopsy findings	Laboratory findings	Treatment
Disdier P, et al.9	France	Female	21	Vasculitis	CK=normal	Prednisolone 1 mg/kg/day, 0.5 mg/kg/day + azathioprine
	France	Female	26	Vasculitis	CK=normal	Prednisolone + cyclophosphamide
Gilliam JH 3rd, et al.7	Israel	Male	19	Vasculitis	CK, LDH, AST=normal	Prednisolone 60 mg/day
Ménard DB, et al.6	Australia	Male	44	Granulomatous myositis	CK, rheumatoid factor, ANF=normal	Prednisolone 80 mg/day
Diószeghy P, et al.10	Hungary	Male	41	Granulomatous myositis	CK=normal	No response to steroid or nonsteroid anti-inflammatory medications
Drabble EM, Gani JS11	Australia	Male	50	Not performed	CK, ANF, C3, C4=normal	Prednisolone 30 mg/day
Hall MJ, et al.8	United Kingdom	Female	32	Myositis	CK, antismooth muscle antibodies, antimitochondrial antibodies, ANF, C3, C4, Jo-1=normal	Prednisolone 60 mg/day
Christopoulos C, et al.12	Greece	Female	19	Myositis	CK=normal	Prednisolone 0.5 mg/kg/day
This case study	United States	Male	15	Myositis	CK, aldolase, c-ANCA, p-ANCA, antimyeloper-oxidase antibody, antinuclear antibody direct=normal	Methylprednisolone dose pack 4 mg and then methotrexate 15–20 mg per week

ANF=

antinuclear factor;

AST=

aspartate aminotransferase;

C3=

complement 3;

C4=

complement 4;

c-ANCA=

antineutrophil cytoplasmic antibodies;

CK=

creatine kinase;

LDH=

lactic dehydrogenase;

p-ANCA=

perinuclear antineutrophilic cytoplasmic antibodies.

The previously reported cases of gastrocnemius myalgia linked to Crohn's disease demonstrated occurrence in both genders, ranging from 19 to 50 years of age. The distribution of the muscle histology reported in previous cases showed 2 with granulomatous myositis, 2 with nonspecific myositis, and 3 with vasculitis.¹² To our knowledge, this is the first case reported in the United States. Most cases, as well as our own, displayed normal serum levels of creatine kinase and were negative for c-ANCA. However, a previous report of a 19-year-old female did note a presentation of high titers of c-ANCA at the time of the bilateral calf myalgia.¹²

In conclusion, gastrocnemius myositis is a rare extra intestinal manifestation that may be particularly troublesome or refractory. Our patient required dual therapy (ie, corticosteroids and methotrexate) for a sustained response.