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Eliana MuisFaridin HPCase ReportDepartment of Internal MedicineFaculty of MedicineUniversity of HasanuddinCHRONIC PAIN AND DYSCREPANCY IN A 48 YEAR OLD MALE PATIENT WITH MELORHEOSTOSIS

melorheostosisSclerosing mesodermal disease Non-hereditaryBenign Affects the skeleton and adjacent soft tissue.Derived from Greek:meloslimbrheinto flowosteonboneMainly involves the lower extremity, may also affect the upper extremity, pelvic, costae, and spine Rarely involves the skull and facial bones. Characterized by a classic radiographic feature of hyperostosis periosteal on cortical of long bones resembling dripping candle wax.33

Synonims = Candle wax diseases of the bonesLeris diseaseOsteosis eburnisans monomelica.melorheostosisA rare disease, first described by Leri and Joanny in 1922.Several cases was found incidentally by radiographic.44

Demography of melorheostosisAbout 400 cases have been reported in the literatureAffects 1 in a million peopleMale = femaleNo race predilectionIn approximately 50% of cases dysplasia that occurs in early childhood is manifest by 20 years of age.5

Remains unclear.Loss of mutation function in the LEMD3 gene (MAN1), a protein of the inner nuclear membrane involved in bone morphogenic has been observed.Etiology & Pathogenesis6Chronic pain (neuralgia/arthralgia)Clinical manifestationWith periods of exacerbation & arrestIntensity range from mild to severeLimb stiffnessRestriction of joint movementDeformity

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Clinical manifestationMay involved:segmental & unilateral hemimelic1 bonemonostotic1 limbmonomelicmultiple bonespolyostoticOther disorder has been reported: Mesodermal abnormalities such as hemangioma, nevi, arteriovenosus malformation, glomus tumor.8

Clinical manifestationThe osseus changes can cause functional morbidity.9Skin and subcutaneous tissue involvement: Edema, hyperpigmentation, fibrosis, erythematous, myositis, myosclerosis, muscular atrophy, joint contracture that leads to deformity and limb discrepancy which difficult to treat.Treatment: Conservative and Operative, multidisciplinary involving rheumatologist, medical rehab and orthopaedic specialist.Mr. AS, 48 y.oFrom KendariMarried, has 3 childrenEarly retiredVisited Rheumatology outpatientward at WS hosp. in Feb, 1st 2011MR 455454Case report10

Chief complain: Pain on right knee, over 10 years, not affected by the wheather, with periods of acutely exacerbated by activity such as stair climbing and arrest. He stated the pain felt like cramp and dull, initially. Then turned into sharp and penetrating pain, radiated to the ankle joint, upper thigh and the hip. The pain gradually worsen since 2 years before, accompanied by limb stiffness, leads to restriction of movement on walking, hardly without any help.History taking11Initially, he went for traditional medicine. As he began hardly walk, he went to an internist who stated that he suffered from osteoporosis and was given Voltaren 2x50 mg. Up till recently, he has been consuming the medication, not routinely, and without control. He reported no fever, cough or shortness of breath.No nausea or vomiting. Still, he has had loss of appetite since 2 years before, result in decrease of BW about 5 kg.No complained of urinating and defecation.History taking12History of trauma 3 years before, which he fell from a motorcycle. It caused a laceration and tender mass on his right knee, which healed after he went for traditional medication. There was also, lacerations on the right ankle.No history of heart disease, HT, and diabetes. No history of the same disorder in his family.History taking13Physical examination14Moderately ill, well nourished, composmentisBW 49 kg, BH 156 cm, BMI 20.13 kg/m2BP 120/70 mmHg, P 78 x/min, RR 16 x/min, axillary temp 36.7oCNo abnormalities found on his head, neck, thorax, or abdomen.GALS examination15GaitAsymmetricWaddling gaitNot able to turn quicklyInspection from behindMild scoliosisParaspinal muscular normal and symmetricShoulder and gluteal muscular normal and symmetricIliacal height asymmetric (right higher than left)No popliteal edemaInspection from lateralTouch toesPalpationCervical and lumbal lordosis normalMild thoracic kyphosisSpine and hip flexion not max (30o)Pain on lumbar area of supraspinatus, and right hipGALS examination16ArmsArms behind head

Arms straightHands in front

Turn hands over

Make a fistFingers on thumbPalpationGlenohumeral, sternoclavicular and acromioclavicular joints movement normalElbow extension maximal No edema/deformity on wrist & fingers Fingers extension maximal Supination/pronation normal, palmar normal (no edema, muscular wasting & erythematous)Fist strength normalFine precision normal/agilePain on metacarpal (-)GALS examination17Legs

Lying on a couchAsymmetric, Edema on right limbDiscrepancy (+)Left hip & knee flexion,internal hip rotation normalRight hip flexion 15o, internal hip rotation abnormal, right knee flexion 30oPain (-) at left hip, (+) at rightPain (-) at left patella, (+) at right, efusion (-)Pain (-) at left metatarsal, (+) at rightPopliteal angle right < leftDorsalis pedis right & left (+) palpableRight and left pedal normal SpineHead on shouldersLateral flexion of cervical normal

18Figure 1. Musculoskeletal examination (legs)Lab examination19Leukocyte6900/mm3Hb13.4g/dlPlatelet275000/mm3ESR7 / 16/mm3RBS104mg/dlUreum17mg/dlCreatinine0.7mg/dlSGOT/SGPT16 / 21mg/dlNa/K/Cl142 / 3.8 / 105mEq/mlALP127 mg/dlECG20Sinus rhythm, heart rate 80 x/min21

Figure 2. Chest X-rayFigure 11. Right & Left pedisClassic radiographic feature22

Fig 3. PelvicFig 4. Femur (AP & lateral view)

23Fig 5. Right & left popliteal Fig 6. Right & left knee joint (lateral)

24Fig 7. Right knee joint (lateral)Fig 8. Left knee joint (lateral)

25Fig10. Right & left cruris (Lateral)Fig 9. Right & left cruris (AP)

26DIAGNOSISMelorheostosisTREATMENTMeloxicam 15 mg/dayCalcium 2 tab/dayInformed & Educated about progression, tx, complication, & prognosisReferred to medical rehab & orthopaedic specialist.27DISCUSSIONHypothesisSclerotome - Murray & Mc Credie (1979)Melorheostosis lesion may correspond to a sclerotome, which partially reflect the monomelic tendency.Mosaicsm - Fryns (1995)Post zygotic mesenchymal mutation reflect the sporadic bone dysplasia, also changes of vascular, adjacent soft tissue & fair distribution of gender.2728

This patient has monomelic manifestationMonomelic presentation 66-81%Campbell et al8 of 14 patients was monomelicMorris et al81% of 131 patients was monomelic 2829Classic radiography is sufficient enough to diagnose MelorheostosisCT-scan and MRI are not needed in the vast majority of casesBone scintigraphy reveals abnormal increased tracer uptake in the bone and soft tissue lesion

2930Hyperostosis periosteal along the cortex of long bones resembling melting wax flowing down the side of a candle (the dripping candle wax sign)

RADIOGRAPHY FEATUREOsteoma-like appearance with hyperostosis located either on the outer or inner aspect of the affected boneOsteopathia striata-like pattern, which showed long & dense hyperostotic striations near the inner side of the cortex in 2 or more bonesMyositis ossificans-like ossifications in the soft tissue in 2 or more bones unilateral with/without intraosseous hyperostosis.Pathognomonic:Freyschmidt describe additional criterias:3031RADIOGRAPHY FEATURE

Osteoma-like appearance2. Osteopathia striata-like pattern3. Myositis ossificans-like pattern3132In later stages of the disease, endosteal hyperostosis may be seen, and this can partially or completely obliterate the medullary cavity. Even may be bone overgrowth.This patient has cortical & endosteal hyperostosis on right ilium, femur, patella tibia, fibula, talocalcaneal, tarsal-metatarsal & phalanx resembling later stages.

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33Although a relatively benign disease, the osseous changes can be debilitating.Some patients remain asymptomatic, until found incidentally by radiopraphic examination.The majority has chronic pain (neuralgia/arthralgia), limb stiffness, and restriction of joint movement.Severe cases result in discrepancy or soft tissue contracture.Freyschmidt (2001) review of 23 cases, found that the severity of symptoms correlates with the degree of hyperostosis & number of bones involved, with normal lab.33

34This patient complain chronic pain on the right knee, over 10 years, with periods of acutely exacerbation and arresRadiographic feature of cortical & endosteal hyperostosisHistory of trauma could precipitated the disease progression resulted in limb discrepancyMonomelic manifestationSevere case of Melorheostosis34

35Lab result of this patient was normal.There is no definitive lab test for melorheostosis.One case showed elevated serum ALP, and this was thought to be associated with an increase in osteoblastic activity.LABORATORIUM EXAMINATION35

36OsteochondromaParosteal osteosarcomaOsteoid osteomaOther sclerosing bone dysplasia:OsteopoikilosisOsteopathia striataMyositis ossificansDIFFERENTIAL DIAGNOSIS3637

Osteoid osteomaOsteochondromaParosteal osteosarcoma

3738OsteopoikilosisOsteopathia striata

Myositis ossificans38

39TREATMENTEach patient of Melorheostosis is uniqueMajority treated symptomatic.Surgery for the sole purpose of relieving pain is rarely effective, unless that pain is a direct result of nerve pressure or irritation.The patient & family must have a clear understanding of the risks and benefits involved and clear also realistic expectation about the proposed procedures.www.melorheostosis.org39

40BisphosphonateNSAIDNifedipinTREATMENT OPTIONPhysical therapySerial casting/splintNerve block/symphatectomyPharmacologyNon-pharmacologyKonservativeOperativeTendon shorteningFibrous & osseous tissue excisionFasciotomyCapsulotomyCorrective osteotomyBone debulkingAmputation40

41A case report with severe pain on the back and limb + ALP Treated successfully with Bisphosphonate infusion 6 days.Female, 42 yo, with burning pain on thigh that restricted her daily activityTreated effectively with Nifedipine, a vasodilator, for 6 months.Male, 21 yo, suffered from pain & edema on 2nd-4th fingers on left handTreated successfully with ibuprofen 800 mg.

Asian female, 44 yo, with severe Melo that affects ipsilateral limb for over 30 yearsMildly benefits after given Pamidronate 30 mg/day for 3 days & meloxicam 7.5 mg/day for 28 days. 41

42This patients has been taking Voltaren 2x50 mg, not routinelyTreated with Meloxicam 15 mg/day and given also Calcium 2 tablet/dayReferred to ortho specialistReferred to rehab specialist42

43PROGNOSISDespite of functional morbidity, the prognosis usually good.In severe and later stages of case, the prognosis is dubia.43SUMMARY48 yoSuffered from a rare disease, MELORHEOSTOSISChronic pain over 10 years on the right knee with periods of exacerbation & arrest.PE: waddling gait, edema on right side of lower limb, restriction of joint movement, with lower limb discrepancy.

Normal lab result.Classic radiography feature of sclerosing bone dysplasia on right ilium, femur, patella, tibia, fibula, talocalcaneal, tarsal, metatarsal & phalanx with monomelic manifestation.Symptomatic tx: meloxicam 15 mg/day & calcium 2 tab/day.Informed & educated about the progession, comprehensive tx, complication & prognosis.Referred to ortho & med rehab.44

Thank you!45

46The sclerotome forms cartilages and bones4647Cartilage-forming cells migrate from the sclerotome to the limb buds

4748Postzygotic mutations lead to mosaicism

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Example of skin mosaicism4950Types of bone cells

5051Endochondral bone formation

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53What does LEMD3/MAN1 do?Blocks the signal from Bone Morphogenic Proteins (BMPs) and from TGF by binding to SMAD proteinsPreventing SMAD proteins from activating certain genes involved in bone formationThus, loss of LEMD3/MAN1 function leads to excess of bone formation.5354What does LEMD3/MAN1 do?

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