Chronic recurrent multifocal osteomyelitis is also known as Chronic recurring multifocal osteomyelitis.
Chronic recurrent multifocal osteomyelitis (CRMO) is a rare condition (1:1,000,000), in which the bones have lesions, inflammation, and pain. Its definition is evolving. Many doctors and articles described CRMO as an autoimmune disease that has symptoms similar to osteomyelitis, but without the infection. Some doctors thought CRMO was related to SAPHO syndrome. Cutting edge research now classifies CRMO as an inherited auto-inflammatory but have yet to isolate the exact gene responsible for it. Some specialists believe they have discovered a link between CRMO with a rare allele of marker D18S60, resulting in a haplotype relative risk (HRR) of 18. Other experts found that "mutations in LPIN2 cause a syndromic form of chronic recurrent multifocal osteomyelitis known as Majeed syndrome, while mutations in pstpip2 cause a murine form of the disorder. The roles played by LPIN2 and the human homolog of pstpip2, PSTPIP2, in the etiology of chronic recurrent multifocal osteomyelitis are uncertain but are currently being investigated." (10.1097/BLO.0b013e3180986d73. El-Shanti. HI. Ferguson. PJ. Chronic recurrent multifocal osteomyelitis: a concise review and genetic update. Clinical Orthopaedics and Related Research. 462. 11–9. 2007. September. 17496555.). The professional theories seem to be moving in the direction of an inherited gene.
Due to its inflammatory nature, its recurrent outbreaks, and its lack of any known pathogen, CRMO has been reclassified as an inflammatory disease. This particular classification, autoinflammatory diseases, encompasses both hereditary types (Familial Mediterranean Fever, FMF; Mevalonate Kinase Deficiency, MKD; TNF Receptor Associated Periodic Syndrome, TRAPS; Cryopyrin Associated Periodic Syndrome, CAPS; Blau syndrome; Pyogenic sterile Arthritis, Pyoderma gangrenosum and Acne syndrome, PAPA; Chronic Recurrent Multifocal Osteomyelitis, CRMO) and multifactorial disorders (Crohn's and Behçet's diseases). CRMO is not longer considered an autoimmune but rather an inherited, autoinflammatory disease. Chronic: because it does not go away for a long time. Recurrent: because it comes back. It cycles between active and dormant, symptoms and no symptoms, exacerbation and remission. Multifocal: because it can erupt in different sites, primarily bones. Each outbreak can be in a different part of the body. Osteomyelitis: because it is very similar to that disease but appears to be without any infection.
CRMO was once considered strictly a childhood disease, but adults have been diagnosed with it. The disease tends to range from 4 to 14 years old, with 10 years old as its median age. As stated above, CRMO occurs 1:1,000,000 and primarily in girls with a 5:1 ratio. That means out of six million, there will probably be 5 girls and 1 boy with the condition. Yet, it may be more widespread than this.
Laboratory tests may help discover the inflammation: C-reactive protein level, erythrocyte sedimentation rate, level of peripheral leukocytes, ferritin level, Anti-nuclear antibody, antinuclear antibody level, and rheumatoid factor status. Most commonly, however, it is an MRI or bone scan that reveals the inflammation and/or lesions.
A doctor could easily misdiagnose CRMO as muscle spasms or simple inflammation and routinely prescribe anti-inflammatory medicines, which is the normal treatment for CRMO. Many childhood aches and pains are dismissed as growing pains. Parents might not even realize that the child needs to see a doctor. CRMO has deep pain, swelling, and a possible fever but not always. A limp may be falsely considered as the result of an over-active lifestyle. A parent or doctor may not associate a longer limb with CRMO. Without an xray, mri, or bone scan, the bone lesions will go undetected. A child could be misdiagnosed or undiagnosed; take over the counter anti-inflammatory medicines; and live past the illness.
Parents with sick children want a diagnosis, and doctors want to give them one. CRMO may be a catch-all medical phrase for painful bone lesions that do not have a better diagnosis such as arthritis, rheumatic fever, bacterial osteomyelitis, ewing sarcoma, leukemia, lymphoma, rhabdomyosarcoma, neuroblastoma metastasis, eosinophilic granuloma or Langerhans cell histiocytosis. When all the previous illnesses are ruled out and a bone biopsy turns up negative for any known cancer, bacteria, or fungus, CRMO is usually diagnosed.
Regardless of the diagnosis or lack of diagnosis, the patient is suffering from inflammation and possibly intense pain. As such, the most common prescription is for anti-inflammatory medicines such as NSAIDs and steroids. The goal is to rid (or reduce) the body of inflammation and that should ameliorate (or lessen) CRMO. Antibiotics are not commonly prescribed because there is no bacterial or fungal infection. But some doctors do prescribe the antibiotic azithromycin because, in addition to its antibacterial properties, azithromycin also has anti-inflammatory and immuno-modulatory properties.
Schilling and Wagner wrote an article that CRMO (Chronic Recurring Multifocal Osteomyelitis) patients seem to improve greatly with azithromycin. “In one study, 7 out of 13 patients, mainly teenager, showed a fast clinical improvement after they were started on azithromycin. The immediate therapeutic effect of Azithromycin in patients with CRMO was surprising and lead to the hypothesis that azithromycin could have an antiphlogistic in addition to its antibiotic effect in this disease setting…”(http://www.medscape.com/medline/abstract/11142932)
A Malaysian clinic had a very different approach which seems to have worked:
Chiu. CK. Singh. VA. Chronic recurrent multifocal osteomyelitis of the first metatarsal bone: a case report. Journal of Orthopaedic Surgery. 17. 1. 119–22. 2009. 19398809. She (9 yr old girl) underwent curettage through a small oval corticotomy window on the first metatarsal bone. The pain and swelling improved promptly and she was able to walk without pain 2 weeks later. Curettage enabled rapid symptomatic relief and induced remission, with little risk of complications..
"Majeed syndrome is an autoinflammatory disorder consisting of chronic recurrent multifocal osteomyelitis, congenital dyserythropoietic anemia, and neutrophilic dermatosis. To date, two unrelated families with Majeed syndrome have been reported. Mutations in LPIN2 have been found in both families. Here we report a third consanguineous family with Majeed syndrome with a novel mutation. The patient, a 3-year-old Arabic girl, had hepatosplenomegaly and anemia as a neonate. At age 15 months, she developed recurrent episodes of fever and multifocal osteomyelitis. In addition, bone marrow aspiration demonstrated significant dyserythropoiesis (defective red cell formation), suggesting Majeed syndrome. Coding sequences and splice sites of LPIN2 were sequenced in the patient and her mother. A homozygous single-basepair change was detected in the donor splice site of exon 17 (c.2327+1G>C) in the patient; her mother was heterozygous at this site. These data confirm the role of LPIN2 mutations in the etiology of Majeed syndrome." Al-Mosawi, Al-Saad, Ijadi-Maghsoodi, El-Shanti. A splice site mutation confirms the role of LPIN2 in Majeed syndrome. Arthritis & Rheumatism. 56. 3. 960–4. 2007. 10.1002/art.22431.
"Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis, uncommon childhood diseases of unknown cause, occurred in three children (two brothers and a female cousin). Their parents are consanguineous, and the clinical course of their illness was similar. The two brothers also had Sweet syndrome. The association of Sweet syndrome with chronic recurrent multifocal osteomyelitis and congenital dyserythropoietic anemia in this family suggests that these rare conditions may be interrelated."10.1016/S0022-3476(89)80650-X. Majeed. H. Congenital dyserythropoietic anemia and chronic recurrent multifocal osteomyelitis in three related children and the association with Sweet syndrome in two siblings. Journal of Pediatricts. 115. 5, Part 1. 730–4. 1989. November. Kalaawi. M. Mohanty. D. Teebi. A. Tunjekar. M. Algharbawy. F. Majeed. S. Algazzar. A.
Fortunately, CRMO usually resolves itself. Most (but not all) children do not suffer any major lingering or long term disability. Symptoms can be managed. In most cases, the acute outbursts will pass. In the long run, the child can have a normal adult life.
Physical therapy has helped some CRMO patients. Physical therapy works to maintain and/or restore movement and flexibility.