Case Rounds : Case1

by Joan Bathon, M.D.

History of Present Illness

S.M. is a 29 y.o. black Jamaican man who presented to the Johns Hopkins Rheumatology Clinic complaining of difficulty eating due to inability to open his mouth. At age 17 he developed low back pain, morning stiffness and 40 pound weight loss. At age 25 his elbows and knees became swollen and painful. He was admitted to a local hospital and found to have lytic lesions in the mandible, clavicles and patellae; bone biopsies were nondiagnostic and cultures were negative for bacteria, fungus and TB. At age 27 he developed pain and restricted motion in the temporomandibular joints (TMJs). At age 29 he presented to the Johns Hopkins Otolaryngology Clinic because of difficulty with eating and was found to have ankylosis of both TMJs. He was able to maintain his weight by eating pureed food through a straw placed in gaps left by missing teeth. He was scheduled for TMJ arthroplasties but preoperative workup revealed a lytic lesion in his clavicle and marked elevation of Westergren sedimentation rate (ESR). He was referred to Rheumatology Clinic for further evaluation. He denied a history of conjunctivitis or uveitis, heel pain, enteric infections, or psoriasis.

Past Medical History:

  1. Several episodes of dysuria in the past but no urethral discharge or history of sexually transmitted diseases or HIV. Heterosexual with a stable partner.
  2. Severe scarring acne since age 17.
  3. Significant smoking history.

Physical Examination

This was an emaciated young black male in no acute distress with normal vital signs. The general physical examination (chest, cardiovascular and abdominal) was unremarkable. Joint exam was remarkable for complete ankylosis of the TMJs bilaterally, marked limitation of chest expansion, marked limitation of flexion of the lumbar spine (Shober’s 12/10 cm). There was marked tenderness across the entire mandible, both clavicles, the right patella, the right medial malleolus and at multiple costochondral junctions. The toes and the right knee were warm, swollen and tender. Skin exam revealed a diffuse folliculitis/acneiform eruption with extensive scarring involving the face and upper trunk.

Laboratory Studies

Hematocrit 31%; WBC 7,800; platelets 442,000. ESR 90 mm/hr, total protein 9.0 gm/dl, albumin 3.9 gm/dl.

RPR negative, RF negative, ANA negative. SPEP – polyclonal hypergammaglobulinemia. HLA-B27 antigen testing was negative.

Urethral cultures were negative for gonorrhea. Skin biopsy cultures were negative for bacterial and fungal pathogens.

Synovial fluid from the right knee was noninflammatory and was negative for culture of bacterial and fungal pathogens.

Radiology Studies

Figure 1
Bone scan demonstrated increased uptake in the left mid clavicle, right sacroiliac joint, right medial malleolus, both patellae, the sternomanubrial joint, several toes and the entire mandible.(Fig.1)
Figure 2
Radiographs of the pelvis and lumbar spine revealed ankylosis of the right sacroiliac joint and large asymmetric syndesmophytes from T12 to L5.(Fig.2)
Figure 3
Radiographs of the mandible (shown here), left clavicle, and patellae were characterized by expansile lesions with a mixed sclerotic/cystic pattern.(Fig.3)
Figure 4
Radiographs of the feet showed erosions of the right first proximal interphalangeal joint, extensive distal phalangeal osteolysis, and periosteitis of the medial malleolus.(Fig.4)

Differential Diagnosis

1. [ ] Sarcoidosis
2. [ ] Multifocal osteomyelitis
3. [ ] Reiter’s syndrome
4. [ ] Disseminated gonococcal arthritis
5. [ ] Acne arthritis
6. [ ] Fibrous dysplasia
7. [ ] Paget’s disease
8. [ ] Ankylosing spondylitis
9. [ ] Inflammatory bowel disease with spondylitis/sacroiliitis

Discussion

This patient presented with an inflammatory joint and bone process accompanied by acneiform rash and by systemic features including weight loss, high ESR, polyclonal gammopathy, and anemia. His musculoskeletal disease was characterized by asymmetric sacroiliitis and spondylitis, profound osteolysis of the distal phalanges of the feet, and expansile lesions in bones distant from sites of articulation that were characterized by a mixed sclerosis/lytic picture.

Sarcoidosis causes both bone and skin disease. The common cutaneous manifestations are erythema nodosum and painless nodules (noncaseating granulomas), neither of which our patient had. Musculoskeletal presentations of sarcoidosis include acute arthritis and chronic lytic lesions in bones, particularly in the phalanges, due to replacement of bone by granulomas. Our patient had had several bone biopsies which did not show granulomas. Furthermore, Ankylosis of the SI joint and syndesmophytes would be highly atypical for sarcoidosis.

Multifocal osteomyelitis was effectively ruled out at age 25 when multiple bone biopsy cultures were negative for bacteria, fungus and TB.

Seronegative spondyloarthropaties are commonly categorized as follows: 1) ankylosing spondylitis; 2) Reiter’s syndrome or reactive arthritis; 3) inflammatory bowel disease with arthropathy; 4) psoriatic arthritis. Our patient was HLA-B27 negative, had never had uveitis, heel pain, or documented urethritis. His rash was not psoriatic and he had no family history of spondylitis. Our patient clearly has a spondyloarthropathy but it cannot be neatly fit into one of the above four categories.

Disseminated gonococcal arthritis causes acute arthritis but does not cause sacroiliitis and spondylitis. Furthermore, his urethral cultures were negative for gonorrhea.

Fibrous dysplasia is a condition of unknown etiology in which the diaphyses of long bones expand, causing pain, deformity and fracture. This usually presents in female children and is not associated with systemic features or sacroiliitis or spondylitis.

Clinical Course

S.M. was treated with indomethacin. Over the next two months, his joint pain markedly decreased, his weight increased by 4.5 kg, and his ESR decreased to 8 mm/hr. He then underwent bilateral TMJ arthroplasties. Histology of the resected bone and cartilage showed reactive trabecular bone and dense fibrosis. Cultures were negative for bacteria, fungus and TB. Twelve months after the surgery, the patient maintained 30 degrees of motion in the TMJs and was able to eat normally prepared foods. His musculoskeletal pain continued to be well controlled on indomethacin, his ESR remained below 25 mm/hr and his hemotocrit increased to 40%.

DIAGNOSIS: Acne Arthritis

Case Discussion

Our patient’s presentation is consistent with the syndrome known as SAPHO (synovitis, acne, pustulosis, hyperostosis and osteomyelitis), and formerly termed acne arthritis. The syndrome is characterized by severe scarring acne and related conditions; hyperostotic bone lesions (particularly in the clavicles and sternum); sacroiliitis; spondylitis; and, peripheral inflammatory arthritis.

The most common form of acne, acne vulgaris, is not associated with musculoskeletal abnormalities. It is the more severe forms, acne conglobata and acne fulminans, along with hidradenitis suppurativa and dissecting cellulitis of the scalp, that are found in association with the SAPHO syndrome. Most patients are young males and nearly all are HLA-B27 negative. Acne fulminans often presents with systemic features such as fever and weight loss.

Patients with acne conglobata are more likely to have peripheral and axial arthritis, while those with acne fulminans are more likely to have multiple, painful hyperstotic bone lesions. (Our patient had both musculoskeletal manifestations.) The peripheral arthritis is usually symmetrical, and most commonly involves the ankles and small joints of the feet. Axial involvement is manifested by sacroiliitis and spondylitis. Syndesmophytes and coarse paravertebral ossifications are seen, as well as ossification of tendinous insertions, similar to the findings seen in classic seronegative spondyloarthropathies.

The bone lesions of SAPHO are usually lytic-appearing on radiographs, and are most commonly located in the clavicle, sternum, and long bones of the extremities. Biopsies typically show chronic inflammation and fibrosis without evidence for infection. Patients may have elevated serum alkaline phosphatase levels.

The cause of this syndrome remains unclear. Exhaustive investigations to identify a nidus of infection have generally been unrevealing, although there are sporadic reports of propionibacterium from bone cultures in these patients. Another theory is that the syndrome is a reactive arthritis or hypersensitivity syndrome secondary to a skin pathogen or to products of sebum. HLA-B27 positivity does not appear to predispose to this syndrome.

Therapy is oriented towards aggressive control of the acne combined with nonsteroidal antiinflammatory agents for the arthritis and spondylitis. Some patients with acne fulminans may require steroids for control of their systemic symptoms. It should be noted that synthetic derivates of vitamin A, that are used to treat acne, may themselves induce musculoskeletal pain syndromes, skeletal hyperostosis (i.e., osteophytes), and calcification of ligamentous and tendinous insertions. Deciding whether the symptoms and physical findings are due to the underlying disease or its treatment may be complex and may require discontinuation of the drug to see if the symptoms resolve. Whether this arthritis would respond to agents such as methotrexate or antibiotics is unknown.

References

Knitzer RH and Needleman BW. Musculoskeletal syndromes associated with acne. Sem Arthritis Rheum 20:247-55, 1991

Maugars Y, Berthelot JM, Duclous JM, Prost A. SAPHO syndrome: a followup study of 19 cases with special emphasis on enthesis involvement. J Rheumatol 22:2135-41, 1995

Rosner IA, Burg CG et al. The clinical spectrum of the arthropathy associated with hidradenitis suppurtiva and acne conglobata. J Rheumatol 20:684-7, 1993

Chamot AM, Benhamou CL, Kahn MF, et al: Le syndrome acne pustulose hyperostose osteite (SAPHO) – 85 observations. Rev Rhum Mal Osteoartic 54:187-96, 1987

Updated: July 9, 2012

Joan Bathon, M.D.

About Joan Bathon, M.D.

Dr. Bathon was a Co-Deputy Director of the Division of Rheumatology at Hopkins Bayview. She was also the founder and director of the Hopkins Arthritis Center.