By Chris Tehlirain, MD
Postdoctoral Fellow, Division of Rheumatology
Johns Hopkins University School of Medicine.
Release Date: July 13, 2006
Expiration Date: July 13, 2008
Dr. Tehlirian has no significant financial interest or relationships to disclose.
A gentleman comes in complaining of right knee pain. He is a 48-year-old African American man who was transferred from the Infectious Disease Clinic to the Thayer Medical Service for possible septic arthritis. His symptoms essentially limited his right knee motion; he is not able to flex more than 30 degrees. He has had surgery. There is an area medial to the knee that is swollen, and there is an area lateral to the knee that has been draining pus since August 2005. He has some occasional chills, no fevers, and no other systemic manifestations.
He had a diagnosis of severe osteoarthritis that came on over a short period of time. He was complaining of pain in his knees bilaterally. His left knee was replaced in September 2003, and his right hip was replaced in February 2004. The unfortunate thing is that a few months after his right hip replacement, in June 2004, he started having an accumulation of fluid in his right hip. It was then surgically debrided and found to have streptococci of different types, Streptococcus Group F and Streptococcus milleri, growing E. coli and some other bugs. They actually went in twice to clean that out. After the second washing, a rod was placed into the femur, for unclear reasons.
A year later, about June 2005, he still had accumulations of fluid in the area and had to have it cleaned out again. They took out his initial prosthesis because it was infected and put in an antibiotic spacer for about two months, until August 2004; he also received IV antibiotics — mostly ciprofloxacin, vancomycin, and gentamicin — for the bugs that were growing. Unfortunately, he had a distal femoral fracture after the second prosthesis was put in; in August 2004 they had to go in the space and do an open reduction with internal fixation. Since then, he has had recurrent problems with infections of that joint. When seen in the Infectious Disease Clinic, he had obvious pus growing from around the knee joint area and the concern was that it was septic arthritis, so they asked the Assistant Chief of Service of Thayer to admit this gentleman for further workup.
Past Medical History:
He had multiple boils of skin and had taken Keflex or tetracycline for about 25 years, until 2004. He has had eczema in the past. He had hypertension, chronic renal insufficiency of a baseline of 1.4-1.5 creatinine. He also had an EGD showing gastritis in 2000. He never had a GI bleed. His surgical history also included multiple skin grafts to the axillae in 1975. He is allergic to penicillin (but he does not know what happens), and he is also allergic to almonds (but he does not know the reaction); he just stays away from both of them. For medications, he has been taking Aleve over the counter (15 tablets in the morning for the last 25 or 30 years) for stiffness that lasts 1-1.5 hours, Percocet as needed, and Oxycontin (20 mg BID). The Percocet and Oxycontin were started since his hip replacement.
His mother died at 69 of Alzheimer’s. His father had coronary artery disease and died at age 75 from a CVA. He has one sister and two brothers. One of the brothers also had skin boils, but they were not as bad as his.
He has smoked half a pack a day for more than 20 years. No alcohol. He used to use IV drugs (heroin and cocaine) but has been clean for the past 8 years.
Now, this essentially was a gentleman who, if you asked him when was he last healthy, would say it was when he was age 13. He says that at age 13 he started having multiple skin infections, mostly involving the scalp area. He says that when he touched his scalp at any point in time when he was 13 to 15, pus would shoot out from those areas. He was treated with antibiotics, Keflex and tetracycline, for multiple years. In his teens and early 20s, he developed infections, boils, in his axilla, groin, and buttocks — so much so that he had to have skin grafts done in his 20s.
Otherwise, he had no lymphadenopathy, no dry eyes, no dry mouth, no skin rashes other than the infectious issues that he had. For some reason, the skin infections have died down over time. He had them mostly from his teenage years until he was in his 20s. The axillary issues, other than the scalp, had somewhat quieted down since he had the skin graft. He has no photosensitivity, no mouth ulcers. He has never had a sexually transmitted disease. The other interesting thing was that his left knee, left elbow, and right knee also gave him problems from time to time. The swelling would come and go during his teenage years and since, but nobody had ever stuck a needle into them to drain out fluid. His left knee was more of a problem than his right knee, and, just by inference, I would say that is why they replaced the left knee. It is not clear why he developed osteoarthritis within a year’s time.
Below are images from his physical exam.
His pulse is 80, BP 124/83, RR 18, SaO2 100% RA, 90 kg. In general, he is in no distress. He is well-developed man. His HEENT is unremarkable. He has no murmurs on cardiac exam. His abdomen is soft with normal bowel sounds. Extremities show a right knee that is swollen with a 4-cm fluctuant mass, proximal and lateral to the right knee joint, which is where he had a pus culture done. He also had orthopaedics put a needle into his right knee joint to aspirate. His right buttock had multiple areas of open pustules without swelling and drainage, and a lot of scarring. Pain makes the right knee difficult to move, but he is able to move it more than 30 degrees. His left elbow feels a bit warm to the touch but is not swollen, and his extension is about 107. He has chronic skin changes over the scalp, with hair loss in areas where there is scarring. A skin graft is noted in his axilla, with a lot of scarring in his buttocks and groin area as well. Nothing on his palms or his feet.
There’s nothing too remarkable in his labs.
His potassium is a little bit up. His serum creatinine is 1.8, with baseline being around 1.5, most likely resulting from the daily Aleve for the past 25 years. His white count is a little bit up, but not unexpected from the infection in his hip. His sedimentation rate and CRP are obviously elevated. He has 1+ protein in his urine. There are a lot of red blood cells that are presumed to be a little bit of a traumatic tap; otherwise, nothing grew from the synovial fluid of the right knee. Light proteus and pseudomonas grew from the pus that is draining proximate to the knee. His blood culture and urine culture are negative. Interestingly, his urine eosinophil is positive; that also could go along with the Aleve. His HLA-B27 is negative.
His chest X-ray (below) shows he has abnormal sternoclavicular heads.
There is a lot of sclerosis of the internal head leading to chronic inflammation, which is somewhat easier to see in the enlarged version. Essentially, he had a lot of sclerosis at the tip, and it is starting to have a little bit of lysis at the very end of the internal head. That is the only abnormality in the chest X-ray.
The pelvis X-ray below shows his replaced joint.
On his left side joint there are a lot of sclerotic changes around the joint with minimal joint narrowing. On the right, there is a lot of joint narrowing but no sclerosis. On the X-ray of his right knee, below, you can see a prosthesis.
What we are talking about is SAPHO — which stands for Synovitis, Acne, Pustolosis, Hyperostosis, and Osteitis. It goes by 50 different names, including acne arthritis, pustulotic arthro-osteitis, sternoclavicular hyperostosis, and acne-associated spondyloarthropathy. The tale of SAPHO starts somewhere in 1961 with a description of the case of a 14-year-old girl with acne conglobata who starts developing synovitis, specifically in her ankles, that comes and goes. The first thing that was described was actually chronic recurrent multifocal osteomyelitis, which seems to be a cousin disease in SAPHO. Chronic recurrent osteomyelitis was first described in 1978 when an association was noticed between recurrent multiple areas of osteomyelitis in children and young adults. Interestly, approximately 15% to 20% of those children also have skin involvement, the most common being palmoplantar pustulosis. In 1987, a French group described SAPHO for somewhat older folks, meaning teenagers and young adults, who essentially had a chronic occurrence of osteomyelitis along with the skin manifestations. Most of these patients have synovitis with joint pain; they also have bone pain depending on the stage of their osteomyelitis, which is involved in large parts of the bone in children. Commonly, these children are admitted to the hospital for workup for malignancies, evaluating for osteosarcoma and for Ewing’s sarcoma as well, but their biopsy turns out to be osteomyelitis without an infectious cause.
Inclusion and Exclusion Features of the SAPHO Syndrome(2)
- Osteoarticular manifestations of severe acne
- Osteoarticular manifestations of palmoplantar pustulosis
- Hyperostosis with or without dermatosis
- Chronic recurrent multifocal osteomyelitis involoving axial or peripheral skeleton, with or without dermatosis
- Possible association with psoriasis vulgaris
- Possible association with inflammatory enterocolopathy
- Features of ankylosing spondylitis
- Presence of low virulence bacterial infections
- Septic osteomyelitis
- Infectious palmoplantar pustulosis
- Infectious chest wall arthritis
- Palmoplantar keratodermia
- Diffuse idiopathic skeletal hyperostosis
- Osteoarticular manifestations of retinoid therapy
Acne and palmoplantar pustulosis are involved, and hyperostosis and chronic recurrent multifocal osteomyelitis are part of this disease. Exclusions essentially come down to an infectious cause of the osteomyelitis or other infectious causes of skin disease or other explanations of the skin and bone disease. Synovitis commonly affects the anterior chest wall, with sternoclavicular joints being the most commonly involved, in about 63% of SAPHO patients. They can have symmetric or asymmetric involvement of the joints, with one or many joints involved. There is no set rule. They also have involvement of the axial skeleton as well as the peripheral joints. One small difference is, commonly with chronic recurrent osteomyelitis, there is involvement of the jaw joint and the axial skeleton (with the lumbar and thoracic spine), with hyperostosis that may also include involvement with the pelvis, similar to this patient, with sacroiliitis and other parts of the pelvis showing osteitis as well, similar to this patient. SAPHO, on the other hand, tends to involve sternoclavicular joints and peripheral joints more so than chronic osteomyelitis.
The largest case review came from the same French group that described the disease in 1987.(3) The review described 120 patients who were followed for three to four years. The purpose of their study was to look at the prognosis of SAPHO; however, in the process they looked at how many of the patients had axial joint involvement, peripheral joint involvement, and skin involvement. Palmoplantar pustulosis, psoriasis vulgaris, severe acne, and a combination of psoriasis and palmoplantar pustulosis were included. 16% of their patients had no skin involvement whatsoever. The age of onset, 29, varied little. Other skin diseases that can be involved are hydradenitis suppurativa, acne conglobata, pyoderma gangrenosum, dissecting scalp cellulitis, pustular psoriasis, and Sweet’s syndrome, all of these being pseudo abscesses with neutrophilic involvement on the skin. It appears infectious, but there is no infectious agent present. About 15% of cases of chronic concurrent osteomyelitis in SAPHO involve Propionibacterium acne, the bacterium that causes acne. The question is whether this is a part of the pathogenesis and whether there is a need for a low virulence organism to induce this low-grade inflammatory chronic state. However, it is only in 15% of the cases of chronic recurrent osteomyelitis of SAPHO that you get the bacterium on biopsy.
Pustulosis is the most commonly associated skin manifestation of SAPHO, involving the palms and soles with pustular eruptions, as seen in the image below.
It is present in more than 50% of SAPHO patients. In the French group’s review of 120 patients, about 55% of them had palmoplantar pustulosis; about 38% had it on its own, and the rest had palmoplantar pustulosis with another skin manifestation, such as psoriasis or severe acne. Psoriasis can be a part of this in and of itself, again leading to somewhat of a discrepancy on what is SAPHO and where it fits in classification. Severe acne — specifically acne fulminans, acne conglobata, and hidradenitis suppurativa — are associated with SAPHO in about 20% of cases. Hyperostosis, involving mostly the sternoclavicular joints, seems to be a continuum of the osteitis, which is a low-grade inflammation of the bone, hyperostosis being the latter finding of osteitis. Osteitis appears like osteomyelitis with no infectious agent. You may see three different stages with early neutrophilic involvement — 1) sometimes finding the acne’s bacterium early, 2) finding mononuclear cells in the intermediate stage and, 3) sclerotic bone in trabeculae late. If you follow the early signs of sclerosis (image on left below), over time you will see lytic lesions (image on right) within the sclerotic sternoclavicular head.
The pathogenesis is not understood. There seem to be two camps as far as the description of this disease. One theory is it is a seronegative spondyloarthropathy, the other theory says it’s not. Some folks who study psoriatic arthritis believe that SAPHO is a subset of psoriatic arthritis, but the complete pathogenesis is not understood. Whether it is triggered by a pathogen and whether it is an autoimmune phenomenon are also in question.
To evaluate this, you obviously would start with X-rays to evaluate the anterior chest wall and sternoclavicular head involvement. A bone scan is very helpful. As it turns out, a group in Germany(4) evaluated 49 patients with SAPHO and essentially came up with a very specific finding in SAPHO patients. They named it the “Bull Head Sign,” based on its appearance, essentially lighting up of the sternoclavicular heads on Technitium-99 bone scan. Of the 49 patients with SAPHO, 35 had the Bull’s Head Sign, shown clearly in the images below.
Going back to the case report of the 120 SAPHO patients3, the prognosis is very good. It is a chronic disorder with a lot of relapse and remission. Over time, the skin seems to improve and so do the joint manifestations. The only problem is avoiding a lot of iatrogenesis in these patients if you do not have the correct diagnosis, as in the patient described. Treatment consists of nonsteroidals, as a first line of treatment, but many case reports describe low-dose corticosteroids, methotrexate, sulfasalazine, colchicine, and cyclosporine, with varying results. Even tetracycline has been used for the skin manifestations, and reported as improving the skin and thus improving the joints.
The question at this point is: Is SAPHO a separate disease? Essentially, SAPHO appears to be an overlap between multiple diseases, including psoriatic arthritis, acne arthritis, CRMO, and seronegative spondyloarthropathy. Many people think SAPHO is a type of psoriatic arthritis because approximately 20% to 30% of SAPHO patients have psoriasis vulgaris. They also have syndesmophytes, as in our patient. They have sacroiliac involvement. Of all SAPHO patients, about 10% to 13% are HLA-B27-positive. In addition, there are many case reports describing the presence of amphicytes, thought to be present in about 15% of all SAPHO patients. For that reason, there seems to be some overlap in the findings of psoriatic arthritis and SAPHO. Chronic recurrent osteomyelitis, which essentially is a part of SAPHO, but with minute differences. You can find the same exact changes in the bone with sterile osteomyelitis, osteitis, and hyperostosis within this disease, although less frequently do you get involvement of the sternoclavicular heads. Specifically, you get involvement of the clavicular bones, with enlargement in the hyperostosis. The joints are not involved. Chronic recurrent osteomyelitis seems to affect the vertebrae and parts of the pelvis, whereas SAPHO affects the sacroiliac joints and the peripheral joints. To further confuse things, about 20% of chronic concurrent osteomyelitis patients have interval palmoplantar pustulosis and other findings. Also, about 8% of SAPHO patients have inflammatory bowel disease. Perhaps now you can understand why, from about 1961 until 1987 when we had the first case report and description of SAPHO, this disease was given 50 different names.
- Chamot et al. Le syndrome acne pustulose hyperostose osteite. Rev Rheum 1987;54:187-196.
- Benhamou et al. Synovitis-acne-pustulosis-hyperostosis osteomyelitis syndrome (SAPHO). Clin Exp Rheumatol 1988;6:109-112.
- Hayem at al. SAPHO Syndrome: A long-term follow up study of 120 patients. Seminars in Arthritis and Rheumatism 1987;3;159-171.
- Freyschmidt et al. The bullhead sign:scintigraphic pattern of sternoclavicular hyperostosis and pustulotic arthroosteitis. Eur Radiology 1998:8;807-812.
For more information, see Case Rounds One.