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Primary Hypertrophic Osteoarthropathy

Primary Hypertrophic Osteoarthropathy (PHO) / Pachydermoperiostosis (PDP): Comprehensive Research Report

2026-04-22
Falcon MONDO:0016620 Model: Edison Scientific Literature 29 citations

Primary Hypertrophic Osteoarthropathy (PHO) / Pachydermoperiostosis (PDP): Comprehensive Research Report

Executive summary

Primary hypertrophic osteoarthropathy (PHO), also known as pachydermoperiostosis (PDP) or Touraine–Solente–Golé syndrome, is a rare inherited disorder with a characteristic triad of digital clubbing, pachydermia, and periostosis, driven by impaired prostaglandin E2 (PGE2) clearance due to pathogenic variants in HPGD and/or SLCO2A1. The most actionable current therapeutic axis is suppression of prostaglandin synthesis (notably COX-2 inhibition), with evidence of improvement in soft-tissue/joint manifestations and biochemical markers but limited effect on established periostosis. (lu2023primaryhypertrophicosteoarthropathy pages 1-2, li2025twocasesof pages 1-2, lu2023primaryhypertrophicosteoarthropathy pages 7-8)

Table (click to expand)
Domain Summary
Disease names / synonyms Primary hypertrophic osteoarthropathy (PHO); also pachydermoperiostosis (PDP) and Touraine–Solente–Golé syndrome. Clinical forms: complete, incomplete, and forme fruste/fruste (lu2023primaryhypertrophicosteoarthropathy pages 1-2, nicolau2023tourainesolentegolesyndromepathogenic pages 1-2, joshi2019pachydermoperiostosis(touraine–solente–golesyndrome) pages 1-2, cai2025distinctfeaturesof pages 1-2)
Key identifiers Genetic subtypes: PHOAR1 MIM 259100, PHOAR2 MIM 614441, PHOAD MIM 167100. Causal gene IDs: HPGD MIM 601688, SLCO2A1 MIM 601460. MeSH from ClinicalTrials.gov: Osteoarthropathy, Primary Hypertrophic (D010004) (lu2023primaryhypertrophicosteoarthropathy pages 1-2, xu2021monoallelicmutationsin pages 1-2, NCT02438709 chunk 1)
Causal genes & inheritance HPGD loss-of-function causes PHOAR1, classically autosomal recessive; SLCO2A1 biallelic variants cause PHOAR2 (autosomal recessive), and monoallelic SLCO2A1 variants can cause PHOAD (autosomal dominant) with generally milder phenotype and incomplete/sex-skewed penetrance (lu2023primaryhypertrophicosteoarthropathy pages 1-2, xu2021monoallelicmutationsin pages 1-2, li2025twocasesof pages 1-2)
Core mechanism Disease results from impaired PGE2 catabolism: SLCO2A1/OATP2A1 (PGT) mediates cellular uptake of prostaglandins, and 15-PGDH (HPGD) oxidizes PGE2 to PGE-M. Deficiency of either step elevates PGE2, promoting angiogenesis, fibroblast activity, endothelial changes, and abnormal bone remodeling/periostosis (lu2023primaryhypertrophicosteoarthropathy pages 2-4, lu2023primaryhypertrophicosteoarthropathy pages 4-6, li2025twocasesof pages 1-2)
Key biomarkers Urinary PGE2 is elevated across PHO subtypes. In HPGD deficiency (PHOAR1), urinary PGE-M usually decreases and the PGE2/PGE-M ratio rises; in SLCO2A1 deficiency (PHOAR2), urinary PGE-M usually increases and the PGE2/PGE-M ratio is near normal. Reported median urinary PGE2:creatinine in HPGD-related literature review: 627.1 ng/mmol versus 61.49 ng/mmol normal. In one comparison, urinary PGE2 median was 277.58 ng/mmol creatinine in PHOAD vs 473.19 ng/mmol in PHOAR2 (p=0.038) (lu2023primaryhypertrophicosteoarthropathy pages 4-6, li2025twocasesof pages 1-2, xu2021monoallelicmutationsin pages 1-2)
Hallmark clinical triad Digital clubbing + pachydermia + periostosis are the hallmark triad. Clubbing occurs in almost all PHO patients and is often the initial symptom. Periostosis is typically symmetric and often affects long bones (radius, ulna, tibia, metacarpals, metatarsals) (lu2023primaryhypertrophicosteoarthropathy pages 4-6, lu2023primaryhypertrophicosteoarthropathy pages 1-2, nicolau2023tourainesolentegolesyndromepathogenic pages 1-2)
Common additional features Frequent additional manifestations include hyperhidrosis, seborrhea/acne, cutis verticis gyrata, joint swelling/stiffness/arthralgia, acro-osteolysis, anemia, and occasional gastrointestinal involvement. Quantitative data from an HPGD review/case series: hyperhidrosis 60.1%, joint pain 46.1%, joint swelling 37.1%, osteolysis 30.3%, delayed cranial suture closure 16.9%, patent ductus arteriosus 15.7%; median symptom onset 5.1 years, median diagnosis 22.1 years, male:female 2.2:1 (li2025twocasesof pages 4-7, li2025twocasesof pages 1-2, lu2023primaryhypertrophicosteoarthropathy pages 4-6)
GI / systemic complications GI disease is especially linked to SLCO2A1-related PHO. In a Chinese review of 158 patients, 17.2% had gastrointestinal involvement; among those with GI disease, anemia 40.0% vs 4.5%, hypoalbuminemia 16.7% vs 0.9%, myelofibrosis 19.0% vs 0.9% compared with PHO patients without GI involvement; 86.7% (13/15) with GI complications had SLCO2A1 variants (rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4)
Epidemiologic notes PHO is rare; secondary hypertrophic osteoarthropathy accounts for the large majority of HOA overall (~95%), so exclusion of secondary causes is essential. Sex skew varies by subtype: PHOAR1 ~1:1 male:female, whereas PHOAR2/PHOAD are predominantly male; some older reports cite male predominance around 7:1 or 9:1 in clinically defined PDP/PHO cohorts (nicolau2023tourainesolentegolesyndromepathogenic pages 2-5, rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4, lu2023primaryhypertrophicosteoarthropathy pages 4-6, nicolau2023tourainesolentegolesyndromepathogenic pages 1-2, joshi2019pachydermoperiostosis(touraine–solente–golesyndrome) pages 1-2)
Etoricoxib / COX-2 inhibitors Best-supported targeted symptomatic therapy because COX-2 is rate-limiting for prostaglandin synthesis. A 6-month intervention in 41 PHO patients showed significant reduction in urinary PGE2 and clinical remission/improvement of digital clubbing, pachydermia, and arthritic symptoms, but periostosis and anemia did not improve; GI ulcer/bleeding may persist or worsen. A ClinicalTrials.gov study (NCT02438709) evaluated etoricoxib 60 mg daily, enrollment 30, with outcomes including PGE2 at 3 and 6 months, pain VAS, finger volume, and knee circumference (lu2023primaryhypertrophicosteoarthropathy pages 7-8, NCT02438709 chunk 1)
NSAIDs (nonselective) Commonly used for pain and arthritis-related symptoms; can improve joint pain/swelling, morning stiffness, and inflammatory markers, but are palliative and limited by gastrointestinal toxicity, especially problematic in PHO with GI involvement. Some reports note poor response in individual cases (nicolau2023tourainesolentegolesyndromepathogenic pages 2-5, almalki2024pachydermoperiostosisdueto pages 1-2, rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4)
Bisphosphonates Reported as adjunctive treatment for musculoskeletal pain and high bone turnover; evidence is limited to case reports/small series (e.g., pamidronate mentioned in review literature), with rationale to reduce increased bone remodeling rather than correct the upstream prostaglandin defect (li2025twocasesof pages 4-7, li2025twocasesof pages 8-9, rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4)
Lanreotide Evidence limited to a 2024 HPGD splice-variant case report initially mistaken for acromegaly: symptoms responded poorly to NSAIDs but showed excellent response to lanreotide autogel used for ~1 year. This is anecdotal and not established standard therapy (almalki2024pachydermoperiostosisdueto pages 1-2)
Other reported therapies Refractory or supportive options reported in case literature include hydroxychloroquine, tamoxifen, octreotide, colchicine, botulinum toxin A, intra-articular steroids, synovectomy/radiosynoviorthesis, and plastic surgery for severe ptosis/skin changes. Evidence remains low-level and case-based (nicolau2023tourainesolentegolesyndromepathogenic pages 2-5, li2025twocasesof pages 8-9, rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4)

Table: This table condenses the main identifiers, genetics, biomarkers, phenotype spectrum, and treatment evidence for primary hypertrophic osteoarthropathy/pachydermoperiostosis. It is designed for quick knowledge-base population using only the cited context IDs.

1. Disease information

1.1 Definition / overview

PHO is an inherited disorder of skeletal and skin abnormalities, classically presenting with digital clubbing, pachydermia, and periostosis. (lu2023primaryhypertrophicosteoarthropathy pages 1-2, li2025twocasesof pages 1-2)

Recent authoritative definition (2023 review, Frontiers in Endocrinology; published 29 Aug 2023; URL: https://doi.org/10.3389/fendo.2023.1235040): The abstract states: “Primary hypertrophic osteoarthropathy (PHO) is a genetic disorder mainly characterized by clubbing fingers, pachydermia and periostosis.” (lu2023primaryhypertrophicosteoarthropathy pages 1-2)

1.2 Key identifiers (with evidence available in retrieved sources)

Not available in retrieved evidence: MONDO ID, ICD-10/ICD-11 codes, and a verified Orphanet ORPHA code were not explicitly present in the retrieved full-text evidence; they therefore cannot be asserted here without external database verification. (shahin2025theroleof pages 5-5)

1.3 Synonyms / alternative names

1.4 Evidence source type

The information synthesized here is derived from aggregated disease-level review literature (notably a 2023 review) plus primary patient-level evidence (case reports/series and a 2025 systematic review of HPGD-related cases), and a trial registry record (ClinicalTrials.gov). (lu2023primaryhypertrophicosteoarthropathy pages 1-2, li2025twocasesof pages 1-2, almalki2024pachydermoperiostosisdueto pages 1-2, NCT02438709 chunk 1)

2. Etiology

2.1 Disease causal factors

PHO is primarily genetic, caused by impaired PGE2 degradation/transport: * HPGD encodes 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme that oxidizes (inactivates) PGE2. (lu2023primaryhypertrophicosteoarthropathy pages 2-4) * SLCO2A1 encodes OATP2A1 / prostaglandin transporter (PGT), which mediates cellular prostaglandin uptake needed for intracellular degradation. (lu2023primaryhypertrophicosteoarthropathy pages 1-2, lu2023primaryhypertrophicosteoarthropathy pages 2-4)

A two-step clearance model is described: (1) selective uptake across the plasma membrane and (2) oxidation in the cell; deficiency of either elevates prostaglandins. (lu2023primaryhypertrophicosteoarthropathy pages 2-4)

2.2 Genetic risk factors (causal genes, inheritance)

Genetic subtypes/inheritance: * PHOAR1 (AR): caused by HPGD mutation. (lu2023primaryhypertrophicosteoarthropathy pages 1-2) * PHOAR2 (AR): caused by SLCO2A1 biallelic mutation. (lu2023primaryhypertrophicosteoarthropathy pages 1-2) * PHOAD (AD): caused by SLCO2A1 monoallelic pathogenic variants. (lu2023primaryhypertrophicosteoarthropathy pages 1-2, xu2021monoallelicmutationsin pages 1-2)

Authoritative 2021 primary genetics paper (Journal of Bone and Mineral Research; Apr 2021; URL: https://doi.org/10.1002/jbmr.4310): abstract states: “Monoallelic mutations in SLCO2A1 cause autosomal dominant primary hypertrophic osteoarthropathy.” (xu2021monoallelicmutationsin pages 1-2)

2.3 Examples of pathogenic variants (recent/illustrative)

2.4 Environmental risk/protective factors

No robust, disease-specific environmental risk or protective factors were identified in the retrieved evidence; PHO is primarily a monogenic prostaglandin-metabolism disorder. Secondary hypertrophic osteoarthropathy (not PHO) is associated with underlying systemic disease (e.g., malignancy, infections, lung disease), which must be excluded diagnostically. (lu2023primaryhypertrophicosteoarthropathy pages 7-8, rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4)

2.5 Gene–environment interactions

No explicit gene–environment interaction evidence was present in the retrieved texts.

3. Phenotypes

3.1 Core phenotype triad (clinical signs)

3.2 Additional phenotypes (with quantitative data where available)

A 2025 systematic literature review of 89 HPGD-related PHO cases reported frequencies including: hyperhidrosis 60.1%, joint pain 46.1%, joint swelling 37.1%, osteolysis 30.3%, delayed cranial suture closure 16.9%, and patent ductus arteriosus 15.7%. (li2025twocasesof pages 4-7)

Other commonly described manifestations include seborrhea/acne, cutis verticis gyrata, arthropathy, acro-osteolysis, anemia and GI abnormalities. (lu2023primaryhypertrophicosteoarthropathy pages 4-6, xu2021monoallelicmutationsin pages 1-2)

3.3 Onset and progression (temporal development)

  • Onset is often described with peaks postnatally and at puberty, and differs by subtype: PHOAR1 tends to begin earlier (after birth), whereas PHOAR2/PHOAD typically begin in adolescence. (lu2023primaryhypertrophicosteoarthropathy pages 4-6)
  • In the 2025 review of HPGD cases, median symptom onset was 5.1 years but median age at diagnosis was 22.1 years, indicating substantial diagnostic delay. (li2025twocasesof pages 4-7)

3.4 Quality of life impact

Direct quality-of-life instrument data (e.g., SF-36, EQ-5D) were not found in the retrieved evidence. Functional impact is inferred from pain, joint swelling/stiffness, and disfiguring skin changes (including ptosis/cutis verticis gyrata), and from delays in correct diagnosis. (lu2023primaryhypertrophicosteoarthropathy pages 4-6, rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4)

3.5 Suggested HPO terms (non-exhaustive)

Based on described manifestations: * Digital clubbing — HP:0100759 * Pachydermia / skin thickening — HP:0001067 (general) / HP:0008066 (thickened skin; depends on exact mapping) * Periostosis — HP:0002758 * Hyperhidrosis — HP:0000975 * Acne — HP:0001061 * Cutis verticis gyrata — HP:0007539 * Acro-osteolysis — HP:0006046 * Arthralgia — HP:0002829 * Joint swelling — HP:0001386 * Anemia — HP:0001903 * Patent ductus arteriosus — HP:0001643

(li2025twocasesof pages 4-7, lu2023primaryhypertrophicosteoarthropathy pages 4-6, xu2021monoallelicmutationsin pages 1-2)

4. Genetic / molecular information

4.1 Causal genes

4.2 Molecular mechanism (current understanding)

Upstream defect: impaired prostaglandin clearance due to loss of PGT-mediated uptake (SLCO2A1) and/or 15-PGDH-mediated oxidation (HPGD). (lu2023primaryhypertrophicosteoarthropathy pages 2-4)

Biochemical consequence: elevated PGE2; 2023 review states it is “generally accepted” that PGE2 plays important roles in PHO development, and that mutations in either gene impair degradation and elevate PGE2. (lu2023primaryhypertrophicosteoarthropathy pages 4-6)

Downstream signaling: PGE2 signals via EP1–EP4 receptors (GPCRs). The 2023 review highlights EP receptor biology and notes EP4 signaling in particular in skeletal biology (including a proposed sensory nerve EP4 axis). (lu2023primaryhypertrophicosteoarthropathy pages 2-4, lu2023primaryhypertrophicosteoarthropathy pages 4-6)

Cell/tissue-level effects: PGE2 is linked to cell proliferation and angiogenesis seen in histology of clubbing/skin; VEGF is discussed as a mediator whose expression can be stimulated by PGE2. (lu2023primaryhypertrophicosteoarthropathy pages 2-4, lu2023primaryhypertrophicosteoarthropathy pages 4-6)

4.3 Modifier genes / epigenetics / chromosomal abnormalities

No modifier genes, epigenetic mechanisms, or chromosomal abnormalities were identified in the retrieved evidence.

4.4 Suggested GO biological process terms (examples)

(lu2023primaryhypertrophicosteoarthropathy pages 2-4, lu2023primaryhypertrophicosteoarthropathy pages 4-6)

4.5 Suggested Cell Ontology (CL) terms (examples)

Based on described receptor/pathology targets: * Osteoblast — CL:0000062 * Osteoclast — CL:0000092 * Endothelial cell — CL:0000115 * Fibroblast — CL:0000057

(lu2023primaryhypertrophicosteoarthropathy pages 4-6, lu2023primaryhypertrophicosteoarthropathy pages 2-4)

5. Environmental information

PHO is a primary genetic disorder; the retrieved evidence did not identify specific toxins, lifestyle risks, or infectious triggers. Key “environmental” considerations are iatrogenic—e.g., NSAID-related GI risk is clinically relevant, particularly when GI involvement exists. (rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4, lu2023primaryhypertrophicosteoarthropathy pages 7-8)

6. Mechanism / pathophysiology

6.1 Causal chain (high-level)

  1. HPGD or SLCO2A1 pathogenic variants → 2. impaired PGE2 uptake/oxidation (two-step clearance defect) → 3. elevated PGE2 (and altered PGE-M patterns depending on gene) → 4. EP receptor signaling, angiogenesis/VEGF association, fibroblast/endothelial changes, altered bone turnover → 5. digital clubbing, pachydermia, periostosis; joint symptoms and systemic complications in subsets. (lu2023primaryhypertrophicosteoarthropathy pages 2-4, lu2023primaryhypertrophicosteoarthropathy pages 4-6)

6.2 Upstream vs downstream

6.3 Suggested pathway/therapeutic targets

The 2023 review notes COX-2 as the rate-limiting enzyme for prostaglandin production and discusses future possibilities including targeting PGES or blocking prostaglandin action (e.g., EP4 antagonists). (lu2023primaryhypertrophicosteoarthropathy pages 7-8, lu2023primaryhypertrophicosteoarthropathy pages 2-4)

7. Anatomical structures affected

7.1 Organ/system level

7.2 Suggested UBERON terms (examples)

(lu2023primaryhypertrophicosteoarthropathy pages 4-6, rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4)

8. Temporal development

8.1 Onset

8.2 Progression/course

The condition generally progresses slowly, with symptoms often evolving over years and diagnosis frequently delayed into adulthood; substantial diagnostic delay is quantified in the 2025 review (median diagnosis 22.1 years vs onset 5.1 years). (li2025twocasesof pages 4-7)

9. Inheritance and population

9.1 Epidemiology

Robust population prevalence/incidence is not established in the retrieved evidence base. A case report cites “estimated prevalence ~0.16%” and male:female ~7:1, but this estimate is not corroborated by an epidemiologic study in the retrieved set and should be treated cautiously. (joshi2019pachydermoperiostosis(touraine–solente–golesyndrome) pages 1-2)

9.2 Sex ratio and subtype differences

Subtype-specific sex patterns are emphasized: * PHOAR1: male:female ~1:1 (lu2023primaryhypertrophicosteoarthropathy pages 4-6) * PHOAR2/PHOAD: predominantly male in reported series (lu2023primaryhypertrophicosteoarthropathy pages 4-6)

In the HPGD-focused systematic review of 89 cases, male predominance was quantified as male:female 2.2:1. (li2025twocasesof pages 4-7)

9.3 Penetrance/expressivity

PHO shows variable expressivity and can follow recessive or irregular dominant patterns; autosomal dominant familial transmission in 54.4% of families (historical review) is referenced in both the 2023 review and 2021 genetics paper. (lu2023primaryhypertrophicosteoarthropathy pages 2-4, xu2021monoallelicmutationsin pages 1-2)

10. Diagnostics

10.1 Clinical criteria

A specific diagnostic rule (attributed to Borochowitz et al. in a case report) states that PHO/PDP diagnosis should be made when ≥2 of the following are present: (i) family history, (ii) clubbing, (iii) hypertrophic skin changes, (iv) bone pain/radiographic changes. (joshi2019pachydermoperiostosis(touraine–solente–golesyndrome) pages 1-2)

10.2 Laboratory biomarkers

Key biomarkers (urine): * Urinary PGE2 is a key biological indicator and is elevated across subtypes. (lu2023primaryhypertrophicosteoarthropathy pages 4-6) * PGE-M patterns help subtype discrimination: typically decreased in HPGD deficiency and increased in SLCO2A1 deficiency; the urinary PGE2/PGE-M ratio differs by genetic subtype. (lu2023primaryhypertrophicosteoarthropathy pages 4-6)

A 2025 HPGD-case systematic review reported a median urinary PGE2-to-creatinine ratio 627.1 ng/mmol vs 61.49 ng/mmol normal. (li2025twocasesof pages 1-2)

10.3 Imaging

Plain radiographs show periosteal ossification/cortical thickening and may show acro-osteolysis. (nicolau2023tourainesolentegolesyndromepathogenic pages 1-2, lu2023primaryhypertrophicosteoarthropathy pages 4-6)

10.4 Genetic testing approach (real-world implementation)

10.5 Differential diagnosis

Secondary hypertrophic osteoarthropathy is more common (~95% of HOA overall) and must be excluded; additional differentials include acromegaly, thyroid acropachy, rheumatoid/psoriatic arthritis, and juvenile idiopathic arthritis. (rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4, nicolau2023tourainesolentegolesyndromepathogenic pages 1-2)

11. Outcome / prognosis

Mortality and life expectancy data were not identified in the retrieved evidence. Morbidity is driven by chronic pain, joint symptoms, disfigurement, anemia, and GI complications in subsets. Anemia is described as a major complication, potentially related to GI hemorrhage or myelofibrosis. (lu2023primaryhypertrophicosteoarthropathy pages 4-6, rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4)

12. Treatment

12.1 Pharmacotherapy (current practice)

COX-2 inhibition (etoricoxib; highest-quality evidence in retrieved set): * The 2023 review reports that in a 6-month clinical intervention in 41 PHO patients, urinary PGE2 significantly decreased and patients experienced clinical remission of clubbing, pachydermia, and arthritic symptoms, but periostosis was not relieved; anemia and GI issues may not improve. (lu2023primaryhypertrophicosteoarthropathy pages 7-8)

Clinical trial registry evidence (real-world implementation): * ClinicalTrials.gov NCT02438709 (“Application of COX-2 Inhibitor for Treatment of Primary Hypertrophic Osteoarthropathy”; first posted 08 May 2015; sponsor Peking Union Medical College Hospital) describes etoricoxib 60 mg daily with primary outcomes measuring serum PGE2 change at 3 and 6 months, and secondary outcomes including pain VAS and distal finger volume. (NCT02438709 chunk 1)

NSAIDs: commonly used for symptomatic relief; however GI toxicity is an important limitation, especially in those with GI involvement. (nicolau2023tourainesolentegolesyndromepathogenic pages 2-5, rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4)

Bisphosphonates: reported for musculoskeletal pain/high bone turnover, but evidence is largely case-based and not definitive. (li2025twocasesof pages 4-7, rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4)

12.2 Other/experimental or case-based therapies

12.3 Suggested MAXO terms (examples)

  • Cyclooxygenase-2 inhibitor therapy (e.g., etoricoxib)
  • Nonsteroidal anti-inflammatory drug therapy
  • Bisphosphonate therapy
  • Genetic counseling
  • Whole-exome sequencing / molecular genetic testing

(lu2023primaryhypertrophicosteoarthropathy pages 7-8, NCT02438709 chunk 1, li2025twocasesof pages 4-7)

13. Prevention

No primary prevention (in the sense of preventing disease occurrence) is established for monogenic PHO in the retrieved evidence. Practical prevention focuses on: * Genetic counseling, cascade testing in families, and reproductive counseling given recessive/dominant forms. (xu2021monoallelicmutationsin pages 2-3, lu2023primaryhypertrophicosteoarthropathy pages 1-2) * Tertiary prevention: mitigating complications (e.g., monitoring/avoiding GI harms from NSAIDs/COX-2 inhibitors in patients with GI disease; multidisciplinary management to reduce diagnostic delays). (rodriguez2009primaryhypertrophicosteoarthropathy pages 3-4, li2025twocasesof pages 4-7)

14. Other species / natural disease

No naturally occurring veterinary analogs or cross-species susceptibility data were identified in the retrieved evidence.

15. Model organisms

The 2023 review notes major limitations of animal models: HPGD−/− and SLCO2A1−/− mice are not viable postnatally, and pharmacologic modulation of 15-PGDH affects bone/muscle but does not reproduce PHO skeletal phenotype; better models are needed. (lu2023primaryhypertrophicosteoarthropathy pages 7-8)

Recent developments (prioritizing 2023–2024)

  1. 2023 synthesis of genetics, biomarkers, and management: Lu et al. (Frontiers in Endocrinology; 29 Aug 2023; https://doi.org/10.3389/fendo.2023.1235040) provides an updated mechanistic view linking PHO to the prostaglandin metabolic pathway and emphasizes urinary PGE2 and PGE-M profiles for subtype discrimination and monitoring. (lu2023primaryhypertrophicosteoarthropathy pages 2-4, lu2023primaryhypertrophicosteoarthropathy pages 4-6)
  2. 2024 novel HPGD splice variant and nonstandard therapy experience: Almalki et al. (JCEM Case Reports; Nov 2024; https://doi.org/10.1210/jcemcr/luae215) describes a novel splice variant with molecular confirmation and reports clinical improvement on lanreotide autogel. (almalki2024pachydermoperiostosisdueto pages 1-2)

Notes on evidence gaps

  • This report cannot supply a verified MONDO ID, ICD-10/ICD-11 codes, or a confirmed Orphanet ORPHA code, because they were not explicitly present in the retrieved evidence snippets. (shahin2025theroleof pages 5-5)
  • No high-quality epidemiologic prevalence/incidence studies were retrieved; frequency data are therefore drawn mainly from genotype-focused systematic reviews and case series. (li2025twocasesof pages 4-7, joshi2019pachydermoperiostosis(touraine–solente–golesyndrome) pages 1-2)

Key sources (URLs, dates)

References

  1. (lu2023primaryhypertrophicosteoarthropathy pages 1-2): Q. Lu, Yang Xu, Zeng Zhang, Shan-shan Li, and Zhenlin Zhang. Primary hypertrophic osteoarthropathy: genetics, clinical features and management. Frontiers in Endocrinology, Aug 2023. URL: https://doi.org/10.3389/fendo.2023.1235040, doi:10.3389/fendo.2023.1235040. This article has 51 citations.

  2. (li2025twocasesof pages 1-2): Jun Li, Shilei Jia, Jianqun Guo, Wenhui Xie, Yijiao Ma, Xiaojie Gao, and Meihao Gao. Two cases of primary hypertrophic osteoarthropathy caused by hpgd variants: a case report and literature review. BMC Pediatrics, Mar 2025. URL: https://doi.org/10.1186/s12887-025-05590-z, doi:10.1186/s12887-025-05590-z. This article has 1 citations and is from a peer-reviewed journal.

  3. (lu2023primaryhypertrophicosteoarthropathy pages 7-8): Q. Lu, Yang Xu, Zeng Zhang, Shan-shan Li, and Zhenlin Zhang. Primary hypertrophic osteoarthropathy: genetics, clinical features and management. Frontiers in Endocrinology, Aug 2023. URL: https://doi.org/10.3389/fendo.2023.1235040, doi:10.3389/fendo.2023.1235040. This article has 51 citations.

  4. (nicolau2023tourainesolentegolesyndromepathogenic pages 1-2): Rafaela Nicolau, Tiago Beirão, Francisca Guimarães, Francisca Aguiar, Sara Ganhão, Mariana Rodrigues, Ana Grangeia, and Iva Brito. Touraine-solente-gole syndrome: pathogenic variant in slco2a1 presented with polyarthralgia and digital clubbing. Pediatric Rheumatology Online Journal, May 2023. URL: https://doi.org/10.1186/s12969-023-00831-w, doi:10.1186/s12969-023-00831-w. This article has 6 citations.

  5. (joshi2019pachydermoperiostosis(touraine–solente–golesyndrome) pages 1-2): Amir Joshi, Gaurav Nepal, Yow Ka Shing, Hari Prasad Panthi, and Suman Baral. Pachydermoperiostosis (touraine–solente–gole syndrome): a case report. Journal of Medical Case Reports, Feb 2019. URL: https://doi.org/10.1186/s13256-018-1961-z, doi:10.1186/s13256-018-1961-z. This article has 24 citations and is from a peer-reviewed journal.

  6. (cai2025distinctfeaturesof pages 1-2): Xilei Cai, Xiujuan Yang, Pengyue Zhang, Ziyue Dou, Zilian Chen, Chongzhi Zhu, Weiwei Xu, Xinchen Wang, Xiaodan Hong, and Zhenhua Zhang. Distinct features of three clinical subtypes in 533 patients with primary hypertrophic osteoarthropathy. Orphanet Journal of Rare Diseases, Apr 2025. URL: https://doi.org/10.1186/s13023-025-03722-3, doi:10.1186/s13023-025-03722-3. This article has 1 citations and is from a peer-reviewed journal.

  7. (xu2021monoallelicmutationsin pages 1-2): Yang Xu, Zeng Zhang, Hua Yue, Shanshan Li, and Zhenlin Zhang. Monoallelic mutations in slco2a1 cause autosomal dominant primary hypertrophic osteoarthropathy. Journal of Bone and Mineral Research, 36:1459-1468, Apr 2021. URL: https://doi.org/10.1002/jbmr.4310, doi:10.1002/jbmr.4310. This article has 39 citations and is from a highest quality peer-reviewed journal.

  8. (NCT02438709 chunk 1): Effect Observation Study of COX-2 Inhibitor to Treat Primary Hypertrophic Osteoarthropathy. Peking Union Medical College Hospital. 2012. ClinicalTrials.gov Identifier: NCT02438709

  9. (lu2023primaryhypertrophicosteoarthropathy pages 2-4): Q. Lu, Yang Xu, Zeng Zhang, Shan-shan Li, and Zhenlin Zhang. Primary hypertrophic osteoarthropathy: genetics, clinical features and management. Frontiers in Endocrinology, Aug 2023. URL: https://doi.org/10.3389/fendo.2023.1235040, doi:10.3389/fendo.2023.1235040. This article has 51 citations.

  10. (lu2023primaryhypertrophicosteoarthropathy pages 4-6): Q. Lu, Yang Xu, Zeng Zhang, Shan-shan Li, and Zhenlin Zhang. Primary hypertrophic osteoarthropathy: genetics, clinical features and management. Frontiers in Endocrinology, Aug 2023. URL: https://doi.org/10.3389/fendo.2023.1235040, doi:10.3389/fendo.2023.1235040. This article has 51 citations.

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