Primary Hypertrophic Osteoarthropathy (HPOA)

A Case Report

25 yr old Male Progressive enlargement – hands & legs. Increased Skin folds – forehead. Pain – Knee & Ankle Joints, LBA. Fever (+). Burning pain – epigastrium. Driver/non smoker/non alcoholic. Admitted earlier outside & treated as FILARIASIS. Had Anemia – transfused. Driver/non smoker/non alcoholic. Family history:

Case History

Findings: Grade IV clubbing – Pan digital B/L symmetrical enlargement of forearm and leg Widening of Wrist Vitals Normal. Thyroid and breast normal. Cutis Vertis Gyrata (+) Coarse wrinkles over forehead Tylosis & Pseudoptosis (+) Seborrhoea (+), Folliculitis (+) Prominent Naso Labial folds (+) Sparse Axillary & Pubic hair B/L painless knee effusions External genitalia – Normal Systemic examination - Unremarkable

Cutis Vertis Gyrata

Note: 1. Coarse wrinkles over forehead 2. Tylosis 3. Seborrhoea 4. Folliculitis 5. Prominent Naso Labial folds

Note: Sparse hair growth over the Chest and Axilla.

Clubbing

Note: Clubbing in the feet with Symmetric enlargement of both ankles and knees.

Working diagnosis:

1. Hypertrophic oseoarthropathy ? Cause probably primary with bone marrow involvement.

2. Acromegaly3. Pagets disease

WORK UP

Haemogram : Microcytic Hypochromic Anemia

Lymphocytosis ESR – 28 mm/hr RFT – Normal LFT – ALP elevated GTT – Normal TSH – Normal VDRL – Non – Reactive. USG ABDOMEN & SCROTUM – Normal. CT Chest & Abdomen – Normal.

X Rays :-Skull, Chest, Wrist with hand, Chest, Pelvis and Legs with Ankle

• Cortical Expansion

• Sella turcica appears Normal

• Soft Tissue Thickening

• Widening of the ends of the long bones

• Joint Space Normal

• Periosteal Thickening

Normal

• Periosteal thickening

• Joint Space Normal

• Long Bones B/L Symmetrical

• Periosteal thickening

Radiologist opinion:

Differential Diagnosis1. Diaphyseal dysplasia2. Osteodermopathica hypertrophicans3. Touraine Solente Gole syndrome.

Ortho Opinion:

Synovial fluid aspiration which was normal. Advised analgesics and calcium.

Opthalmology Opinion:

Tylosis +, Pseudoptosis +, Myopic Astigmatism +. Prescribed glasses.

Dermatology opinion:

Pachydermoperiostosis or

Touraine solente Gole syndrome.

Skin biopsy obtained from forehead to confirm diagnosis.

Psychiatrist Opinion:

For IQ Assessment. BY Weschler Adult Intelligence scale, His IQ was 100.

Cardiologist opinion:

Normal cardiac status clinically.

ECHO DONE:

Prolapse of AML+. EF 68 %. Intact IAS and IVS. Valves normal.

EGD: Hypertrophic gastric mucosal folds.

Skin Biopsy: – Sections show skin lined by mild hyperkeratosis and

irregular acanthosis, shows hyperkeratotic plugs and pigment incontinence, focal acantholysis and multiple pustules within the epidermis with sebacious hyperplasia.

Gastric Mucosal Biopsy: –Foveolar hyperplasia, tortuosity and cystic changes,

polypoid hyperplasia of the surface epithelium, stromal edema, lymphoid collection, plasma cells and eosinophils seen. Consistent with HYPERTROPHIC GASTROPATHY.

GH and IGF 1 levels normal.

Final Diagnosis:

Primary HypertrophicOsteoarthropathy or Pachydermoperiostosis or Touraine Solente Gole syndrome with

1. Hypertrophic Gastropathy with Sliding Hiatus hernia

2. Synovitis – Knee joint.3. Lumbar spondylosis

Discussion

Hypertrophic osteoarthropathy has 2 forms.

PDP accounts for 5%. HPOA accounts for majority – cardiopulmonary and malignancies.

Pachydermoperiostosis [PDP] Also Known As

Also known as:Audry’s syndrome IBrugsch's syndrome (same condition plus

acromicria)Friedreich-Erb-Arnold syndrome

Roy's syndromeRoy-Jutras syndromeUehlinger's syndrome

described by Hippocrates in 450 BCE and were also observed in skeletons found in Central America.

Primary HOA was first described by Friedrich in 1868 as “hyperostosis of the entire skeleton.

In 1890 Pierre Marie defined it as pneumonic hypertrophic osteopathy.

Touraine, Solente and Golé characterized PDP as a primary form of hypertrophic osteopathy in 1935.

PDP typically begins during childhood or adolescence and progresses gradually over the next 5-20 years before stabilizing.

The male-to-female case ratio is approximately 7:1. PDP is more common in African Americans than in

whites. Life expectancy may be normal.

Transmitted in Autosomal dominant form with incomplete penetrance and variable expression. Even recessive forms occur. Family history can only be traced in around 25% to 38% of cases.

A neurological basis is posited and stimulation of the vagal neural crest has been suggested.

abnormalities in fibroblast functionality have been implicated, along with an increase in the synthesis of collagen fibers.

Platelets, with their potent growth factors, have also been suspected. Alcohol intake aggravates the process

A degree of chromosomal instability is considered possible, as genetic disorders such as xeroderma pigmentosum, ataxia-telangiectasia, and Fanconi anemia, among other diseases, have been described in association with PDP.

Finally, greater cellular hypersensitivity to external stimuli (physical and chemical agents) may explain the predisposition of these patients to develop certain kinds of cancer.

PHO to chromosome 4q33-q34 and identified mutations in HPGD, encoding 15-hydroxyprostaglandin dehydrogenase, the main enzyme of prostaglandin degradation.

Homozygous individuals develop PHO secondary to chronically elevated prostaglandin E(2) levels. Heterozygous relatives also show milder biochemical and clinical manifestations.

Touraine et al described 3 forms of PDP:

(1) a complete form with pachydermia and periostitis (2) an incomplete form with evidence of bone abnormalities but lacking

pachydermia (3) a forme fruste with prominent pachydermia and minimal-to-absent skeletal

changes.

Patients may complain of the following signs or symptoms:

Enlargement of the fingers and the toes Swelling or pain of the large joints Coarsening of facial features Grooves or depressions in the scalp Oily, scaly facial skin Excessive sweating of the palms, soles, or other areas A sensation of warmth or burning in the hands and feet

Examination may reveal the following:

Digital clubbing and/or paronychial thickening may be observed. Coarse facial features may be reminiscent of acromegaly.

Facial skin changes may include sclerodermoid thickening and furrowing of the skin on the forehead and the cheeks. Leonine facies may occur in advanced stages.

Cutis verticis gyrata (undulating grooved and thickened scalp) may become apparent during adolescence.

Seborrheic dermatitis of the face and the scalp may be present. Palmoplantar hyperhidrosis or generalized hyperhidrosis characterized by

shiny and/or wet skin may be observed. Dermatitis of the hands and the feet may be associated with hyperhidrosis. Bilateral blepharoptosis may be present. Facial acne may be present.

Associations:

Gastrointestinal pathology, including gastric carcinoma, Crohn disease, peptic ulcer disease, chronic gastritis, and Ménétrièr disease

Myelofibrosis Gynecomastia Compressive neuropathy Hypoplastic internal genitalia Psoriatic onychopathy Periodontal and alveolar bone abnormalities Spondylolisthesis of the L5-S1 vertebrae Congenital cardiac disease Mental retardation.

Rosenfeld-Kloepfer syndrome, a variant of PDP, is characterized by enlargement of the mandible and/or the maxilla and corneal leukoma.

Currarino idiopathic osteoarthropathy is a juvenile incomplete form of PDP characterized by eczema and wide cranial sutures.

A variant form of PDP restricted to the lower extremities in the absence of digital clubbing or typical skin changes has been described.

Thyroid acropachy may cause diagnostic confusion. Unlike PDP, thyroid acropachy is not painful.

Syphilitic periostosis can result in bony changes and symptoms similar to those seen in PDP.

Lab Studies

Thyrotropin and growth hormone levels. RPR and VDRL should be checked.

Imaging Studies

Radiographs of the long bones reveal subperiosteal new bone formation. Mainly seen in the distal tibia; the fibula; the radius; the ulna; the metacarpals; the phalanges; and, less frequently, the metatarsals. Acro-osteolysis and ossification of the ligaments and interosseus membranes may also occur.

Other abnormalities: Cortical thickening without narrowing of the medullary cavity Enlargement of the paranasal sinuses

Radio nucleotide bone imaging (bone scan) findings: Increased radiopharmaceutical uptake in the diaphyses and the

metaphyses of long bones along the cortical margins. Uptake may result from hyperemia occurring prior to

subperiosteal proliferation. Periarticular regions may also have increased uptake

because of associated synovitis. Scintigraphic findings (such as those described above)

often precede changes noted on radiographs.

Less commonly may involve the mandible, the maxilla, the clavicles, the scapulae, and the patellae.

Medical Care

NSAIDs or corticosteroids.

Surgical Care

Vagotomy may improve the articular pain and swelling associated with PDP. Plastic surgery may improve the appearance of the face and scalp by excising

redundant skin and correcting the cutis verticis gyrata. Bilateral blepharoplasties, tarsal wedge resections, excision of skin furrows, and facial rhytidectomy have been described as methods of providing cosmetic improvement.

Patient Education

Genetic counseling to patients and their families.

Thank you…