Shelley and Rawnsley first described piezogenic pedal papules (PPP) in 1968. At that time, they were described as small papular herniations of subcutaneous tissue into the skin of the medial aspect of each heel that occurred only upon standing or upon application of pressure to the sole. They coined the term "piezogenic" meaning "producing pressure;" however, this idiom is used loosely as the pressure triggers the lesions not the other way around. Subsequently, reports of piezogenic wrist papules and muscle herniation of the lower legs in isolation or coexisting with PPP have been introduced into the literature.  These lesions appear to have identical histology to the previously described PPP. Given the diversity of pathology, the term piezogenic papules without specific reference to "pedal" has been used. An infantile variant also exists, and it lacks the piezogenic component.  
Piezogenic papules do not appear to have a hereditary transmission in the vast majority of cases. No direct link has been made to a specific connective tissue defect or condition. It should be noted that the literature has noted an anecdotal associated in groups of patients with both Ehlers–Danlos syndrome and Prader-Willi syndrome presumably due to weakness in collagen, although no specific mechanism has been proven.  
Several risk factors have been identified although, once again, no direct cause has been established. At-risk individuals include patients who are obese, those who have pes planus, and people who have occupations which require long periods of standing. It is frequently found in athletes such as figure skaters or those who participate in long-distance running or high-impact sports. 
Piezogenic papules are very common in the United States and worldwide. Lesions are not typically painful, and therefore, before the establishment of this diagnosis, lesions often went unnoticed. As it stands, diagnosis is often made incidentally or not at all, and therefore, the actual incidence and prevalence of this condition are likely severely underreported.
Studies have shown the incidence of PPPs in the United States to be as high as 76%, with wrist papules in 86% of cases. This appears consistent with a worldwide incidence reported in another study noted 80% incidence of pedal papules, 86% of wrist papules and 74% presenting with both pedal and wrist papules. No evidence of geographic, socioeconomic, or racial predilection. These lesions do appear to be more common in females when compared to males.
Most cases appear to occur spontaneously. However, there have been reports of cases occurring in successive generations within the same family suggestive of a possible autosomal dominant inheritance pattern. Despite this finding, no direct hereditary trigger has been identified. Lesions occur at any age from infancy to adulthood. An unusual infantile variant, termed infantile pedal papules, occurs in non-weight-bearing infants, is characterized by larger nodules on the medial aspect of the heel. The incidence of infantile papules in one study noted to be 6% in newborns and 39% in infants.
The specific etiology of PPP is unknown. However, the mechanism of pressure from standing or application of pressure to the heal inducing herniation of fat into connective tissue in the dermis of the heels is easily replicated. One hypothesis is that elevated pressures may induce small tears in the plantar fascia, thereby creating a defect for herniation of the deep subcutaneous fat. In cases associated with collagen disorder, such as Ehlers-Danlos syndrome, a structural abnormality of the connective tissue has been suspected but not proven
Typically, a biopsy is not necessary for the diagnosis because clinical history and physical exam provide enough to confirm the diagnosis. However, when a lesion is biopsied, specimens of piezogenic papules typically demonstrate hyperkeratosis, degeneration of the thin fibrous septa between fat lobules, and subsequent coalescence of fat. Of note, hyperkeratosis is more prominent in painful lesions, and likely less prominent or absent in asymptomatic lesions. Some studies have also noted a thickened and dense dermis and/or loss of the normal small fat globules in the lower dermis, subcutis, and periadinexally. Occasionally, overt protrusion of enlarged fat lobules into the dermis has been noted. 
In contrast, infantile pedal papules appear as well-defined lobules of mature fat in the mid and deep dermis. Frequently, these fat lobules will be encased in collagen especially the periadinexally around the eccrine glands.
Piezogenic papules most often present asymptomatically, but they may become painful. History alone may not be helpful unless the papules are painful. Painful papules should prompt inquiry into repetitive use and occupational and sporting activities. Awareness of this condition can prove very helpful in a patient with elusive pain who may not have noticed the protrusions.
On exam piezogenic pedal papules present with a firm, yellowish to skin-colored papules that protrude from the lateral, posterior, or medial aspects of the heel. The papules become more prominent when the patient stands in a full weight bearing position and by definition resolve when the patient removes weight. Lesions typically occur bilaterally. Similar lesions have been noted on the ventral wrist then the pressure is applied to the palm of the hand. Many patients will develop both pedal and wrist lesions. Most recently, in addition to pedal and wrist papules, a case of muscle herniation of the lower legs that coexists with piezogenic pedal papules has also been reported.
Infantile pedal papules present in non-weight bearing infants as larger nodules on the medial aspect of the heel.
No further diagnostic tests or treatment are considered necessary as clinical exam alone is sufficient for diagnosis. However, it is important to maintain suspicion for these lesions and to have the patient bear weight to observe the papules; otherwise, the lesions can be easily overlooked. At times, an unusual presentation may confound the diagnosis. One proposed tool for a correct diagnosis is the use of high-frequency ultrasound (US) to confirm findings on exam. On ultrasound, isoechoic lesions within the underlying subcutaneous cellular tissue will be seen. US provides an easy non-invasive means to confirm the diagnosis.  Should there be any doubt in the diagnosis, a biopsy should always be considered a viable alternative, especially should suspicion of alternative diagnosis remain a concern. 
No treatment is typically necessary. However, if lesions become painful, conservative management including behavioral modification, weight loss, avoidance of prolonged standing, and reduced foot trauma should be considered first. Subsequently, compression stockings, heel cups, and orthotics can be used. More invasive techniques should be reserved for refractory cases. Intralesional injections of betamethasone and bupivacaine have been reported with some promise in patients with Ehlers-Danlos syndrome. Lastly, surgical excision may be necessary if lesions are severely painful. A recent case report of successful treatment with deoxycholic acid injection. 
Piezogenic papules represent a fairly distinct entity. A physical examination easily illustrates PPP and typically does not result in diagnostic confusion. Having a patient stand to evaluate pedal papules or placing pressure on their palm to unveil lesions on the volar wrist usually confirms the condition.
Infantile pedal papules have been described under many different names including pre-calcaneal congenital fibrolipomatous hamartomas, bilateral congenital adipose plantar nodules, benign anteromedial plantar nodules of childhood, congenital piezogenic-like pedal papules, bilateral congenital fatty heel pads, and pedal papules of the newborn. These many names can complicate the terminology; however, all are thought to represent the same physiology. It is important to distinguish the entity from juvenile aponeurotic fibroma which typically presents a fixed, solitary, firm subcutaneous nodule which occurs most often in young children or adolescents and is more common on wrists than ankles. If the clinician is concerned a patient has juvenile aponeurotic fibroma papules, plain radiograph imaging will show stippled calcifications. 
Prognosis with this condition is very good. Most patients do not experience pain. Thus, the condition is primarily a cosmetic concern. If patients are in pain, clinicians should have them limit activity and provide occupational and recreational therapy if necessary. 
Piezogenic pedal papules are common and typically asymptomatic, however, may cause patients significant distress. Coordination of care and reassurance are critical. Patients may present to various specialties dermatologist, orthopedic surgery or primary care for evaluation of these lesions. Care to avoid unnecessary invasive treatment for these lesions. Coordination with nursing staff and physical therapy to assist behavioral modifications, taping and more conservative management are ideal.
|||Painful feet due to herniation of fat., Shelley WB,Rawnsley HM,, JAMA, 1968 Jul 29 [PubMed PMID: 5694945]|
|||Piezogenic wrist papules: a common and asymptomatic finding., Laing VB,Fleischer AB Jr,, Journal of the American Academy of Dermatology, 1991 Mar [PubMed PMID: 2061438]|
|||Disappearing subcutaneous papules and nodules: Characteristic features of muscle herniation and piezogenic pedal papules., Mai Y,Nishie W,Sugai T,Imafuku K,Arita K,Shimizu H,, The Journal of dermatology, 2017 Dec [PubMed PMID: 28815687]|
|||Infantile pedal papules., Greenberg S,Krafchik BR,, Journal of the American Academy of Dermatology, 2005 Aug [PubMed PMID: 16021133]|
|||[Pedal papules in newborn infants]., Larralde de Luna M,Ruiz León J,Cabrera HN,, Medicina cutanea ibero-latino-americana, 1990 [PubMed PMID: 2214934]|
|||Piezogenic pedal papules during Prader-Willi syndrome., Schepis C,Greco D,Siragusa M,Romano C,, Journal of the European Academy of Dermatology and Venereology : JEADV, 2005 Jan [PubMed PMID: 15649213]|
|||Painful piezogenic pedal papules in patients with Ehlers-Danlos syndrome., Kahana M,Feinstein A,Tabachnic E,Schewach-Millet M,Engelberg S,, Journal of the American Academy of Dermatology, 1987 Aug [PubMed PMID: 3624559]|
|||Bender TW 3rd, Cutaneous manifestations of disease in athletes. Skinmed. 2003 Jan-Feb; [PubMed PMID: 14673322]|
|||Schlappner OL,Wood MG,Gerstein W,Gross PR, Painful and nonpainful piezogenic pedal papules. Archives of dermatology. 1972 Nov; [PubMed PMID: 4635806]|
|||Usefulness of High-Frequency Ultrasound in the Diagnosis of Piezogenic Pedal Papules., Rodríguez-Bandera AI,Alfageme Roldán F,Hospital-Gil M,de Lucas Laguna R,, Actas dermo-sifiliograficas, 2015 Sep [PubMed PMID: 25708654]|
|||A nonsurgical approach to painful piezogenic pedal papules., Doukas DJ,Holmes J,Leonard JA,, Cutis, 2004 May [PubMed PMID: 15186050]|
|||Turkmani MG, Piezogenic pedal papules treated successfully with deoxycholic acid injection. JAAD case reports. 2018 Jul; [PubMed PMID: 29998180]|