DISCUSSION

The diagnosis of alkaptonuria may be suspected by an accurate physical examination. Dark pigmentation on sclera and on ear cartilage is typically described [6], but not so easy to find in these patients. The classic clinical triad of alkaptonuria is homogentisic aciduria, ochronosis and ochronotic arthropathy [7]. Overall, the incidence of ochronotic arthropathy in patients with alkaptonuria is low [2]. Antimalarial treatment and use of skin-creams containing hydroquinone are important differential diagnosis with exogenous ochronosis [8]. Differential diagnosis must be done with ankylosing spondylitis and degenerative osteoarthosis [7]. However, certain radiologic findings allow its differentiation, like unusual sites of joint involvement (severe glenohumeral joint disease in the absence of significant trauma, advanced changes in the sacroiliac joints and symphyseal joints), and joint-space loss with an unusual pattern (symmetrical joint-space narrowing in the hips and shoulders, and isolated lateral femorotibial loss of knee joint space) (Figure 4). Involvement of large peripheral joints usually occurs about 10 years after spinal changes [7]. Darkening of the urine is a common diagnostic feature and should be considered in children even producing it unusually [2]. Diagnosis can be confirmed using gas liquid chromatography, thin-layer chromatography, or enzymatic spectrophotometry to analyse the amount of homogentisic acid in the patient’s urine. Arthroscopy has been found to be an effective diagnostic tool in cases of suspected ochronosis [2].

For septic arthritis, it is strongly recommended immediate antibiotic therapy and evacuation of purulent material as often as necessary. However, few published data are available that addresses the most effective methods of evacuating this purulent material. Gächter et al. [9] defends that the degree of debridement required according to the intraoperative stage of the joint. Our open approach was based on bad clinical stage of the high-risk patient and radiographic osteolysis, classifying in stage IV. In these cases, open arthrotomy is recommended to effectively eradicate the infection in one-time surgery, with debridement, removal of loose fragments and curettage the cysts. When patients’ symptoms lasting four to ten days, Kirchhoff et al. [10] treated them by open surgery or were converted from arthroscopy to open debridement due to advanced stages. Arthroscopic treatment is also indicated with septic arthritis on native knees with low reinfection rate and good functional outcomes [11]. Although, Aim et al. [12] showed that 25% required more than one arthroscopic lavage and factors significantly associated with arthroscopic treatment failure were Gächter stage III or IV and positive drainage-fluid cultures after 24 h. It’s consensual that all incisions must be closed completely (no drains) and an aggressive early range of motion postoperatively must be routinely emphasized. Another controversy theme is the empiric antibiotic. Current antibiotic choices should be made based on the likely etiological organisms (geographic variation and resistance patterns) and subsequently modified in light of culture and sensitivity results. Our choice is justified by UK guidelines on initial antibiotic choice [13]. Fusidic acid may also be considered as an adjunct because of apparently good penetration into bone [13]. Although it should be noted that MRSA is gradually emerging and has been recently reported a prevalence of up to 17% [10]. With regard to the choice of antibiotic, a multidisciplinary approach with microbiologists is essential.

Currently, there is no proven therapy or prophylactic treatment for alkaptonuric patients [2,4]. Treatment options are administration of non-steroidal anti-inflammatory drugs, intake of preparations containing glucosamine and chondroitin sulphate, intra-articular injection of hyaluronic acid and steroids, arthroscopic debridement of the affected joint and arthroplasty. Treatment is generally supportive and aimed at preventing or minimizing the effects of ochronotic arthropathy, like others arthritis. More specific, the antioxidant properties of vitamin C have been shown to help slow the conversion of homogentisic acid to its pathologic polymeric intermediate [2,6]. Dietary restrictions of foods containing phenylalanine and tyrosine have been shown to be effective in limiting symptoms of ochronotic arthritis because this reduces the production of homogentisic acid. Vitamin E and N-acetyl cysteine are potential therapies because of their scavenging of free radicals and consequent limitation of oxidative damage to joint tissue [2]. The drug nitisinone is being researched as the first potential treatment for alkaptonuria; in previous research it was shown to reduce the levels of HGA by up to 95% [6]. In our patient, we focus the challenge to decide which tissue were infected or simply with dark pigmentation. Sometimes it was difficult to know until where we should do the debridement. This is the second case described in literature with infection and ochronosis, but there not seems to have any relationship between them [4]. The immunocompromised system and injection on the knee must have acted as risk factors for septic arthritis in this case. The joint destruction in these complex patients (with adenocarcinoma, ochronosis arthropathy and septic arthritis) was analysed carefully and it was chosen a non-aggressive management. Other therapeutic strategies could also have been considered according to the literature. Arthroplasty performed in patients with ochronotic arthropathy suggests that the procedure is effective in the alleviation of joint pain and the improvement of mobility [2], even in shoulders [3]. However, it was declined this option because he is still doing antineoplastic treatments, and there is no benefit in some surgery or even infiltration. About prognosis, patients with alkaptonuria can expect a normal life.

Nevertheless, the complications of debilitating arthritis, chronic kidney disease and ochronotic skin alterations will occur [6].

CONCLUSION