The Schnitzler’s syndrome is a rare and underdiagnosed entity which is considered an acquired/late onset auto-inflammatory disease with a median age of onset of 51 years (male
Chronic recurrent multifocal osteomyelitis (CRMO) is also a rare entity and the most severe form of chronic nonbacterial osteomyelitis [
In 1998, a 58-year-old man presented himself with chronic ostealgia, night sweat, and pruritic urticarial lesions on the extremities and trunk in a hospital. At that time, bone scintigraphy showed an increased tracer uptake on both sides of the distal femora, the pertrochanteric region as well as the sacroiliac joints. After excluding an infectious cause a bone biopsy of the left proximal femur was conducted. On the basis of the histopathologic findings, the diagnosis of a chronic recurrent multifocal osteomyelitis was made. Accordingly, the patient was treated with nonsteroidal anti-inflammatory drugs with up to 10 g metamizole sodium for the past 13 years.
In February 2011, the patient was referred to our hospital with distinct ostealgia, night sweat, an unclear weight loss of 6 kg in the last 6 month and pruritic urticarial lesions on the extremities and trunk. The patient described a pain level of 9 on a pain scale of 1 to 10.
However, as the chronic recurrent multifocal osteomyelitis is an uncommon diagnosis in elderly people, we reevaluated the previous diagnosis.
To sum up the pathologic findings, the laboratory investigations showed an increased level of C reactive protein (CRP) (6,98 mg/dL), leuocytosis (11,4 G/L), IL-6 elevation (30,6 pg/mL), and minor IgM elevation (596 mg/dL). Radiological findings in the abdominal CT scan showed a marginal enlargement of the intra-abdominal and inguinal lymph nodes. In the T1-weighted images and in the Short Time Inversion Recovery (STIR) images, MRI showed a diffuse bone marrow infiltration of low-to-intermediate signal intensity as well as cortical thickening and periostal bone apposition without surrounding soft tissue reaction in both femora, both tibiae, both clavicles, the left distal fibula, the right os sacrum, both acetabuli, the left os ilii as well as the right os ischii. A conventional bone radiograph of the most painful left femur revealed subtle periosteal reaction along the lateral aspect of the distal metaphysis. A bone biopsy of the left distal femur showed a sclerotic bone marrow involvement, as well as plasma cells, mast cells, sporadic segmented granulocytes and histiocytes, and a lack of suggestive signs of malignancy. The skin biopsy showed a superficial dermal and perivascular infiltrate of neutrophils.
Together, we found no indications for a malignant tumor or inflammatory bowel disease causing the clinical symptoms of systemic inflammation.
The V198M mutation causing the so-called cryopyrin-associated periodic syndromes in infants could not be found [
Based on these findings, the diagnosis of Schnitzler’s disease was made.
Daily treatment with 100 mg anakinra s.c. was initiated. In the course of treatment, the pruritic urticarial lesions disappeared after 48 hours. After one week, the inflammation parameters normalized, and after four weeks pain therapy was no longer required. Despite all clinical improvements, the 8-week followup of Schnitzler’s syndrome by MRI showed only a slight regression of the bone marrow changes and cortical reactions.
CRMO and Schnitzler’s syndrome are diagnosed by exclusion. At first sight, both diseases can be similar in their manifestation. However, considering the patient as a whole, the age of onset, the male gender, and the very atypical pruritic urticarial lesions on the trunk led to the correct diagnosis. CRMO is associated with pustulosis palmoplantaris, whereas Schnitzler’s disease is associated with neutrophilic dermatitis. Laboratory findings in both syndromes reveal elevated inflammation parameters, but pathognomonic for Schnitzler’s disease is an IgM gammopathy. Histopathologic findings of bone biopsies suggest that osteomyelitis is neither characteristic for CRMO nor for Schnitzler’s syndrome. The most affected bones in adult CRMO patients as well as in Schnitzler’s disease patients are the distal femora and the proximal tibiae [
Hence, Schnitzler’s disease is an important differential diagnosis to CRMO in adults presenting with signs suggestive of CRMO.