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Hypertrophic osteoarthropathy, primary, autosomal dominant(PHOAD)

MedGen UID:
382429
Concept ID:
C2674695
Disease or Syndrome
Synonyms: PACHYDERMOPERIOSTOSIS, AUTOSOMAL DOMINANT; PDP, AUTOSOMAL DOMINANT; PHO, AUTOSOMAL DOMINANT; PHOAD
 
Gene (location): SLCO2A1 (3q22.1-22.2)
 
Monarch Initiative: MONDO:0008172
OMIM®: 167100

Definition

Autosomal dominant primary hypertrophic osteoarthropathy (PHOAD) is characterized by 3 major features: digital clubbing, periostosis, and pachydermia. Patients may also experience joint swelling and pain, and some have reported gastrointestinal symptoms, including watery diarrhea. Males are more commonly affected, and more severely affected, than females (Lee et al., 2016; Xu et al., 2021). Touraine et al. (1935) recognized pachydermoperiostosis (PDP) as a familial disorder with 3 presentations or forms: a complete form with periostosis and pachydermia, an incomplete form without pachydermia, and a forme fruste with pachydermia and minimal skeletal changes. Genetic Heterogeneity Autosomal recessive forms of PHO have been reported (see 259100), including PHOAR2E (614441), which is also caused by mutation in the SLCO2A1 gene. Patients with autosomal recessive PHO do not experience gastrointestinal symptoms. [from OMIM]

Clinical features

From HPO
Knee pain
MedGen UID:
65421
Concept ID:
C0231749
Sign or Symptom
An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) localized to the knee.
Elevated urinary prostaglandin E2 level
MedGen UID:
411843
Concept ID:
C2749457
Finding
An increased amount of prostaglandin E2 in the urine.
Clubbing of fingers
MedGen UID:
3129
Concept ID:
C0009080
Finding
Terminal broadening of the fingers (distal phalanges of the fingers).
Secretory diarrhea
MedGen UID:
75635
Concept ID:
C0267557
Disease or Syndrome
Watery voluminous diarrhea resulting from an imbalance between ion and water secretion and absorption.
Periosteal thickening of long tubular bones
MedGen UID:
322394
Concept ID:
C1834345
Finding
Thickening of the periosteum of long bone.
Seborrheic dermatitis
MedGen UID:
19912
Concept ID:
C0036508
Disease or Syndrome
Seborrheic dermatitis is a form of eczema which is closely related to dandruff. It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk.
Acne
MedGen UID:
152379
Concept ID:
C0702166
Disease or Syndrome
A skin condition in which there is an increase in sebum secretion by the pilosebaceous apparatus associated with open comedones (blackheads), closed comedones (whiteheads), and pustular nodules (papules, pustules, and cysts).
Hyperhidrosis
MedGen UID:
5690
Concept ID:
C0020458
Finding
Abnormal excessive perspiration (sweating) despite the lack of appropriate stimuli like hot and humid weather.
Thickened skin
MedGen UID:
66024
Concept ID:
C0241165
Finding
Laminar thickening of skin.
Cutis gyrata of scalp
MedGen UID:
78095
Concept ID:
C0263417
Disease or Syndrome
The presence of convoluted folds and furrows formed from thickened skin of the scalp, resembling cerebriform pattern. The scalp has convoluted and elevated folds, 1 to 2 cm in thickness. The convolutions generally cannot be flattened by traction.
Ptosis
MedGen UID:
2287
Concept ID:
C0005745
Disease or Syndrome
The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Professional guidelines

PubMed

Lu Q, Xu Y, Zhang Z, Li S, Zhang Z
Front Endocrinol (Lausanne) 2023;14:1235040. Epub 2023 Aug 29 doi: 10.3389/fendo.2023.1235040. PMID: 37705574Free PMC Article
Tran TH, Luu BT, Pham AD, Luong LH, Nguyen LTN, Nguyen BN, Van Nguyen H, Bui TH, Ta VT, Van Tran K
J Clin Rheumatol 2021 Dec 1;27(8S):S739-S740. doi: 10.1097/RHU.0000000000001524. PMID: 32833909
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J Rheumatol 2015 Nov;42(11):2211-4. doi: 10.3899/jrheum.150364. PMID: 26523041

Recent clinical studies

Etiology

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Ding J, Li B, Chen T, Hao L, Li D
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Diagnosis

Lucas Rocha M, Silvestre-Teixeira V
N Engl J Med 2024 Apr 4;390(13):1218. doi: 10.1056/NEJMicm2309119. PMID: 38598576
Lu Q, Xu Y, Zhang Z, Li S, Zhang Z
Front Endocrinol (Lausanne) 2023;14:1235040. Epub 2023 Aug 29 doi: 10.3389/fendo.2023.1235040. PMID: 37705574Free PMC Article
Ikeda K, Miyamori D, Hirabayashi R, Ito M
QJM 2022 Sep 22;115(9):611-612. doi: 10.1093/qjmed/hcac147. PMID: 35731213
Yadav N, Yanamandra U
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Therapy

Biswas S, Narang H, Rajput MS, Makharia G
BMJ Case Rep 2022 May 17;15(5) doi: 10.1136/bcr-2021-247193. PMID: 35580956Free PMC Article
Prasad A, Shahi P, Sehgal A, Bhagirathi Mallikarjunaswamy M
BMJ Case Rep 2020 May 13;13(5) doi: 10.1136/bcr-2020-236034. PMID: 32404375Free PMC Article
Jagdish RK, Bhatnagar MK, Malhotra A, Aggarwal R, Shailly
J Assoc Physicians India 2019 Sep;67(9):87-90. PMID: 31561698
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Prognosis

Alban JJ, Arango-Ramirez A, Olave-Rodriguez JA, Nastasi-Catanese JA, Rodriguez LX
Cold Spring Harb Mol Case Stud 2023 Dec;9(4) Epub 2024 Jan 10 doi: 10.1101/mcs.a006291. PMID: 37591693Free PMC Article
Yap FY, Skalski MR, Patel DB, Schein AJ, White EA, Tomasian A, Masih S, Matcuk GR Jr
Radiographics 2017 Jan-Feb;37(1):157-195. Epub 2016 Dec 9 doi: 10.1148/rg.2017160052. PMID: 27935768
Munichandrappa P, Singh N, Thappa DM
Indian J Dermatol Venereol Leprol 2016 Jan-Feb;82(1):57-8. doi: 10.4103/0378-6323.172901. PMID: 26728812
Ali N
JAAPA 2015 Jun;28(6):65-6. doi: 10.1097/01.JAA.0000462058.86000.b6. PMID: 25989437
Ding J, Li B, Chen T, Hao L, Li D
Aesthetic Plast Surg 2013 Apr;37(2):464-7. Epub 2013 Jan 30 doi: 10.1007/s00266-013-0062-z. PMID: 23361957

Clinical prediction guides

Xu Y, Zhang Z, Yue H, Li S, Zhang Z
J Bone Miner Res 2021 Aug;36(8):1459-1468. Epub 2021 May 5 doi: 10.1002/jbmr.4310. PMID: 33852188
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Stone OJ
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Recent systematic reviews

Palui R, Sridharan K, Sahoo J, Suryadevara V, Kamalanathan S, Naik D, Halanaik D, Durgia H, Raj H
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Marangu D, Gray D, Vanker A, Zampoli M
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Wang Q, Li YH, Lin GL, Li Y, Zhou WX, Qian JM, Xia WB, Wu D
Orphanet J Rare Dis 2019 Dec 26;14(1):297. doi: 10.1186/s13023-019-1264-5. PMID: 31878983Free PMC Article
Shakya P, Pokhrel KN, Mlunde LB, Tan S, Ota E, Niizeki H
J Dermatol Sci 2018 Apr;90(1):21-26. Epub 2017 Dec 28 doi: 10.1016/j.jdermsci.2017.12.012. PMID: 29305259

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