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 Table of Contents  
CASE REPORT
Year : 2016  |  Volume : 5  |  Issue : 1  |  Page : 51-54

Primary hypertrophic osteoarthropathy (Touraine-Solente-Gole Syndrome) in newborn: A rare orthopedic condition seen in newborn


1 Department of Neonatology, Fernandez Hospital, Hyderabad, Telangana, India
2 Department of Pediatrics, Durgabai Deshmukh Hospital and Research Center, Hyderabad, Telangana, India
3 Department of Pathology, N.K.P. Salve Medical College, Nagpur, Maharashtra, India

Date of Web Publication6-Jan-2016

Correspondence Address:
Deepak Sharma
Department of Neonatology, Fernandez Hospital, Hyderabad, Telangana
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/2249-4847.173275

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  Abstract 

Primary hypertrophic osteoarthropathy (PHO), known with various name, is a very rare syndrome, seen infrequently in clinical practice and presents with a wide spectrum of diverse radiological and clinical features in the patient. PHO was first described by Friedreich in 1868 with typical words of “excessive growth of bone of the entire skeleton.” The further classification of different form was done by Touraine, Solente, and Golé in 1935 and they described PHO as the primary form of bone disease. We report an infant who was diagnosed as a case of PHO.

Keywords: 15-hydroxyprostaglandin dehydrogenase gene, primary hypertrophic osteoarthropathy, Touraine-Solente-Gole syndrome


How to cite this article:
Sharma D, Pawar SR, Bharathi S, Shastri S. Primary hypertrophic osteoarthropathy (Touraine-Solente-Gole Syndrome) in newborn: A rare orthopedic condition seen in newborn. J Clin Neonatol 2016;5:51-4

How to cite this URL:
Sharma D, Pawar SR, Bharathi S, Shastri S. Primary hypertrophic osteoarthropathy (Touraine-Solente-Gole Syndrome) in newborn: A rare orthopedic condition seen in newborn. J Clin Neonatol [serial online] 2016 [cited 2021 Apr 14];5:51-4. Available from: https://www.jcnonweb.com/text.asp?2016/5/1/51/173275


  Introduction Top


Primary hypertrophic osteoarthropathy (PHO) is a rare genodermatosis and is hereditary bone disease characterized by traid of digital clubbing, periostosis, and pachydermia.[1] Here we report a newborn that was diagnosed to have PHO immediately after birth.


  Case Report Top


A term female infant was born to a nonconsanguineous couple, G3P2A1L1 mother, through normal vaginal delivery with birth weight of 2.5 kg. The infant had a normal Apgar score of 7, 8, and 9 at 1, 5, and 10 min, respectively. The mother had her first pregnancy terminated in view of neural tube defect. This present pregnancy was a spontaneous conception with adequate folic acid supplementation. At birth, infant was diagnosed to have hypertrophy of medial 3 fingers of right upper limb with thickening of overlying skin and clubbing [Figure 1],[Figure 2],[Figure 3]. There was no simultaneous involvement of gastrointestinal (GI) system, cardiovascular system, or respiratory system in the infant. There were no facial abnormalities and also there was no abnormality of joint movements. The infant was investigated with echocardiography and brain ultrasound, whole body X-ray which was normal except for the periostosis of the affected fingers. The infant was evaluated with growth hormone and thyroid hormone assay which showed normal values leading to rule out endocrinal cause of finger hypertrophy. Vitamin A level of the infant was normal that ruled out hypervitaminosis as a cause of hypertrophy. X-ray of hands showed periostosis of the affected fingers. Urinary levels of PGE2 were increased and genetic analysis showed mutation of 15-hydroxyprostaglandin dehydrogenase (HPGD) gene. There were no other malformations associated with the infant. The infant was discharged and was lost in follow-up.
Figure 1: Hypertrophy of medial three fingers of right upper limb with thickening of overlying skin and clubbing

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Figure 2: Hypertrophy of medial three fingers of right upper limb with thickening of overlying skin and clubbing

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Figure 3: Hypertrophy of medial three fingers of right upper limb with thickening of overlying skin and clubbing

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[Figure 1],[Figure 2],[Figure 3] shows hypertrophy of medial 3 fingers of right upper limb with thickening of overlying skin and clubbing.


  Discussion Top


Primary hypertrophic osteoarthropathy (PHO, MIM 167100) also known as pachydermoperiostosis or idiopathic hypertrophic osteoarthropathy or Touraine-Solente-Gole syndrome is a rare genetic disorder that affects both bones and skin. The important features of this disease includes pachydermia (thickening of the skin), periostosis (excessive bone formation), and finger clubbing (swelling of tissue with loss of normal angle between nail and nail bed).[1] The first scientific case report of PHO was by Friedreich in 1868 in which they reported two affected brothers as “hyperostosis of the entire skeleton.”[2] In 1935, Touraine, et al. labeled PHO as an distinct entity and propagated as the primary form of the hypertrophic osteoarthropathy, which was different from the secondary hypertrophic osteoarthropathy (SHO), that is always associated with an underlying cause (e.g., pulmonary or cardiac disease). In the index patient, there was no associated cardiac or pulmonary disease that ruled out SHO.[3]

It has a very rare incidence with lack of precise incidence and prevalence and is predominantly autosomal dominant in inheritance, although few cases of autosomal recessive and X-linked inheritance have also reported.[4],[5] Males are more commonly associated than females.[6]

The age of disease onset has a bimodal distribution with two different peaks including 1st year of life and at puberty. It is usually considered to be a self-limiting disease. After the active phase during adolescence, its clinical features usually becomes static or may even resolve spontaneously.[7] PHO predominantly affects soft connective tissue, skin, and bone. Digital clubbing and the arthralgia show the involvement of soft connective tissue. Digital clubbing is the universal sign seen in all the patients of PHO. Arthralgia or arthritis is seen in 20–40% of all the cases. The most common joints involved are knees, ankles, and wrists.[8] The involvement of skin comprises two parts: Dermal hypertrophy and glandular hypertrophy. The various bone manifestation includes shaggy periosteal new bone formation of the long bones (periostosis). The radiological examination shows acro-osteolysis, periosteal changes of the short and flat bones, and ossification of ligament and interosseous membranes. According to the range of the tissue involvement, three clinical subtypes have been proposed:

  1. Complete form was seen in around 40% of the patients. Also, known as full-blown phenotype. Clinical features involves pachydermia, periostosis, and finger clubbing
  2. Incomplete form was seen in around 54% of the patients. Here, predominantly bone involvement is there with rare dermatological involvement
  3. Fruste form was seen in around 6% of the patients. Here, predominantly skin involvement is there with rare bone involvement.[9]


According to the recent molecular findings, PHO has been recently categorized into hypertrophic osteoarthropathy, primary, autosomal recessive, type 1 (PHOAR1; OMIM 259100), which is a result of HPGD deficiency and hypertrophic osteoarthropathy, primary, autosomal recessive, type 2 (PHOAR2; OMIM 614441), which is a result of solute carrier organic anion transporter family, member 2A1 (SLCO2A1) deficiency.[10],[11]

The major complications of PHO include anemia, myelofibrosis, hypoalbuminemia, and GI abnormalities (including peptic ulcer, chronic gastritis, gastric carcinoma, Ménétrier's disease, and Crohn's disease).[12] The mechanism of anemia has been proposed to be multifactorial in PHO and various causes includes blood loss from the GI tract, bone marrow failure by myelofibrosis or narrowing of the medullary spaces, and the presence of an inhibitor for erythropoiesis.[13]

Histological studies have shown vascular hyperplasia, endothelial cell activation, edema, and periosteal proliferation.[14] Many researchers all over the globe has reported that patients with PHO and SHO have high levels of vascular endothelial growth factor (VEGF).[15],[16] VEGF induces vascular hyperplasia, new bone formation, and edema and these are characteristic features of hypertrophic osteoarthropathy.[17] Therefore, VEGF is postulated as the prototypical osteogenic-angiogenic coupling factor in the pathogenesis of hypertrophic osteoarthropathy. VEGF cytokine has been proposed to play a major role in the pathogenesis of Crohn's disease, myelofibrosis, and POEMS syndrome. In these conditions too, there is a marked increase in VEGF level and many patients of PHO develop these conditions in the latter phase of life.[18]

The differential diagnosis which must be excluded in neonates includes endocrinal causes such as acromegaly, myxedema, and hypothyroidism; generalized cortical hyperostosis (van Buchem disease); epiphyseal dysplasia; diaphyseal dysplasia, and Hypervitaminosis A.[19] Hormone level measurement helps in differentiating endocrinal cause from PHO. Secondary hypertrophic pulmonary osteoarthropathy because of GI system, cardiovascular system, and respiratory causes can be ruled out by detailed examination and looking for associated manifestation of affected systems. Elevated level of urinary PGE2 is also used as an early laboratory marker for PHO.[10] Treatment involves nonsteroidal anti-inflammatory drugs (NSAIDs) and corticosteroids for relieving pain and swelling. NSAIDs are also effective in reducing sweating and sebaceous gland secretion. Bisphosphonates that are potent inhibitor of osteoclastic bone resorption are used to decrease the bone resorption and remodeling.[20] The mechanism of action is still unknown but there are few case reports of symptomatic relief of hypertrophic osteoarthropathy with use of intravenous pamidronate or zoledronic acid.[21],[22] Skin manifestations are treated with retinoids and colchicine. Corticosteroids has been used to treat myelofibrosis in some patients.[23] Surgical intervention is required for improving the facial appearance.[24]


  Conclusion Top


PHO is a very rare disease which must be thought when there is hypertrophy of the fingers. Although male are commonly affected, female can also be affected and differential diagnosis must be ruled out. Urinary levels of PGE2 are increased and genetic analysis of the patient shows mutation of HPGD gene and are confirmative for diagnosis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Castori M, Sinibaldi L, Mingarelli R, Lachman RS, Rimoin DL, Dallapiccola B. Pachydermoperiostosis: an update. Clin Genet 2005;68:477-86.  Back to cited text no. 1
    
2.
Friedreich N. Hyperostose des gesammten skelettes. Virchows Arch 1868;43:83-7.  Back to cited text no. 2
    
3.
Touraine A, Solente G, Gole L. Un syndrome osteodermopathique: La pachydermie plicaturee avec pachyperiostose des extremites. Presse Med 1935;43:1820-4.  Back to cited text no. 3
    
4.
Rimoin DL. Pachydermoperiostosis (idiopathic clubbing and periostosis): Genetic and physiologic considerations. N Engl J Med 1965;272:923-31.  Back to cited text no. 4
[PUBMED]    
5.
Oikarinen A, Palatsi R, Kylmäniemi M, Keski-Oja J, Risteli J, Kallioinen M. Pachydermoperiostosis: analysis of the connective tissue abnormality in one family. J Am Acad Dermatol 1994;31:947-53.  Back to cited text no. 5
    
6.
Gómez Rodríguez N, Ibáñez Ruán J, González Pérez M. Primary hypertrophic osteoarthropathy (pachydermoperiostosis). Report of two familial cases and literature review. Reumatol Clin 2009;5:259-63.  Back to cited text no. 6
    
7.
Guyot-Drouot MH, Solau-Gervais E, Cortet B, Deprez X, Chastanet P, Cotten A, et al. Rheumatologic manifestations of pachydermoperiostosis and preliminary experience with bisphosphonates. J Rheumatol 2000;27:2418-23.  Back to cited text no. 7
    
8.
Martinez-Lavin M. Miscellaneous non-inflammatory musculoskeletal conditions. Pachydermoperiostosis. Best Pract Res Clin Rheumatol 2011;25:727-34.  Back to cited text no. 8
    
9.
Sinha GP, Curtis P, Haigh D, Lealman GT, Dodds W, Bennett CP. Pachydermoperiostosis in childhood. Br J Rheumatol 1997;36:1224-7.  Back to cited text no. 9
    
10.
Uppal S, Diggle CP, Carr IM, Fishwick CW, Ahmed M, Ibrahim GH, et al. Mutations in 15-hydroxyprostaglandin dehydrogenase cause primary hypertrophic osteoarthropathy. Nat Genet 2008;40:789-93.  Back to cited text no. 10
    
11.
Zhang Z, Xia W, He J, Zhang Z, Ke Y, Yue H, et al. Exome sequencing identifies SLCO2A1 mutations as a cause of primary hypertrophic osteoarthropathy. Am J Hum Genet 2012;90:125-32.  Back to cited text no. 11
    
12.
Jajic I, Jajic Z, Grazio S. Minor but important symptoms and signs in primary hypertrophic osteoarthropathy. Clin Exp Rheumatol 2001;19:357-8.  Back to cited text no. 12
    
13.
Saigal R, Kansal A, Mittal M, Singh Y, Ram H. Pachydermoperiostosis with myelofibrosis and empty sella. J Assoc Physicians India 2010;58:253-5.  Back to cited text no. 13
    
14.
Narayanan S, Mohamed Gani VM, Sundararaju V. Primary hypertrophic osteoarthropathy with hypertrophic gastropathy. J Clin Rheumatol 2010;16:190-2.  Back to cited text no. 14
    
15.
Silveira LH, Martínez-Lavín M, Pineda C, Fonseca MC, Navarro C, Nava A. Vascular endothelial growth factor and hypertrophic osteoarthropathy. Clin Exp Rheumatol 2000;18:57-62.  Back to cited text no. 15
    
16.
Watanabe O, Arimura K, Kitajima I, Osame M, Maruyama I. Greatly raised vascular endothelial growth factor (VEGF) in POEMS syndrome. Lancet 1996;347:702.  Back to cited text no. 16
    
17.
Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Endocr Rev 2004;25:581-611.  Back to cited text no. 17
    
18.
Martinez-Lavin M, Vargas A, Rivera-Viñas M. Hypertrophic osteoarthropathy: a palindrome with a pathogenic connotation. Curr Opin Rheumatol 2008;20:88-91.  Back to cited text no. 18
    
19.
Rastogi R, Suma GN, Prakash R, Rastogi UC, Bhargava S, Rastogi V. Pachydermoperiostosis or primary hypertrophic osteoarthropathy: A rare clinicoradiologic case. Indian J Radiol Imaging 2009;19:123-6.  Back to cited text no. 19
[PUBMED]  Medknow Journal  
20.
Nguyen S, Hojjati M. Review of current therapies for secondary hypertrophic pulmonary osteoarthropathy. Clin Rheumatol 2011;30:7-13.  Back to cited text no. 20
    
21.
Jayakar BA, Abelson AG, Yao Q. Treatment of hypertrophic osteoarthropathy with zoledronic acid: case report and review of the literature. Semin Arthritis Rheum 2011;41:291-6.  Back to cited text no. 21
    
22.
King MM, Nelson DA. Hypertrophic osteoarthropathy effectively treated with zoledronic acid. Clin Lung Cancer 2008;9:179-82.  Back to cited text no. 22
    
23.
Ninomiya S, Hara T, Tsurumi H, Kanemura N, Kasahara S, Ogawa Y, et al. Myelofibrosis successfully treated with prednisolone in a patient with pachydermoperiostosis. Intern Med 2011;50:2207-11.  Back to cited text no. 23
    
24.
Monteiro E, Carvalho P, Silva A, Ferraro A. Frontal rhytidectomy: a new approach to improve deep wrinkles in a case of pachydermoperiostosis. Plast Reconstr Surg 2003;112:1189-91.  Back to cited text no. 24
    


    Figures

  [Figure 1], [Figure 2], [Figure 3]


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