Knuckling down on knuckle pads

By Warren R. Heymann, MD
April 1, 2020
Vol. 2, No. 13

Today is April Fools’ Day. Thus far, 2020 has felt like April Fools’ Year. All of us are dealing with COVID-19, 24/7. During World War II, morale was lifted by the song “There’ll be bluebirds over the White Cliffs of Dover” looking forward to the war’s end when peace would rule over Britain’s iconic cliffs. (This was popularized by Vera Lynn, who is still performing at 103! Just days ago “the Forces’ Sweetheart” invoked England to “keep smiling and keep singing.”) For the past two weeks, DWI&I has devoted itself to the COVID-19 pandemic. Information is coming at us from every angle and is kept up-to-date on the coronavirus section of the AAD website, the CDC website, and innumerable other sources. At this juncture, we would like to offer DWI&I as a respite, looking forward to the day when COVID-19 is a memory. Should there be any compelling reason for COVID-19 commentary, we will be there. For now, if possible, take a short mental break and look beyond the pandemic. Stay safe.

A frustrated patient with knuckle pads (KP) pleaded with me to come up with a solution for his embarrassing problem. I promised him that I would knuckle down and review the latest literature to see if there are any new management strategies for this benign, but aggravating, condition.

KP (aka Garrod’s nodes), may be idiopathic, genetic, or acquired. Primary KP need to be differentiated from secondary KP, so-called “pseudo-KP” (PKP). PKP are trauma-induced, with friction causing KP-like calluses over the interphalyngeal joints; certain professions, such as boxers or carpet layers, are at risk. Those who chew on their knuckles, or have trauma to the regions, as in bulimic patients, may present with PKP. PKP tends to improve by eliminating the inciting factors, in combination with topical therapy. (1,2)

Although initially described by Garrod in 1892, KP have been recognized for centuries. Michelangelo depicted KP on many of his classic works, including the statue of David in Florence and the Sleeping (Dying) Slave in the Louvre. (3) KP usually appear between 15 and 30 years of age, persisting throughout adulthood. (1) There is an equal sex incidence (4), and KP is observed in all races and age groups. KP are characteristically diagnosed clinically, being differentiated from scars, keloids, calluses, clavi, verrucae, fibromas, and giant cell tumors of the tendon sheath. Inflammatory disorders (granuloma annulare, gouty tophi, rheumatoid nodules, Heberden and Bouchard nodes of osteoarthritis, foreign body reactions, and erythema elevatum diutinum) may all resemble KP. (5,6) Histologically, KP are characterized by acanthosis, hyperkeratosis, and “plump” fibroblasts in an initial proliferative phase, becoming more fibrotic as lesions mature. (1)

Virtually all familial cases of KP are associated with other fibromatoses or syndromes. Palmar fibromatosis (Dupuytren’s contracture), plantar fibromatosis (Ledderhose disease), and penile fibromatosis (Peyronie disease) may all manifest KP. Rarely, these disorders may occur simultaneously, known as polyfibromatosis. (6) The association of KP, keratoderma, leukonychia, mixed sensorineural and conductive deafness defines the Bart-Pumphrey syndrome. (5) Barrick et al recently reported the case of an 11-year-old boy with coexisting acrokeratoelastoidosis and KP. (7)

Regarding the pathogenesis of KP, some recent studies raise intriguing hypotheses. The autosomal recessive PLACK syndrome (Peeling skin, Leukonychia, Acral punctate keratosis, Cheilitis and Knuckle pads) results from loss-of-function mutations in the CAST gene encoding calpastatin, a specific inhibitor of calpains. Calpains, functioning as calcium-dependent cysteine proteases, are involved in multiple cellular processes, including cell proliferation, migration, wound healing, apoptosis, and regulation of epidermal cell differentiation. A proposed mechanism underlying PLACK syndrome is that the absence of a functional calpastatin prevents the inhibition of calpains leading to elevated keratinocyte apoptosis and skin hyperkeratosis. (8,9)

Saylam Kurtipek et al evaluated patients with KP (n=47) compared to age and sex-matched controls (n=46); there was a non-significant trend of KP patients to have the metabolic syndrome, although in the KP group there was a significant association with abdominal obesity and hypertension. The authors theorized that insulin-like growth factors in KP patients could cause proliferation of keratinocytes and dermal fibroblasts.

Treating KP is notoriously difficult; PKP is more amenable to therapy. Aside from behavioral modification for PKP, for both KP and PKP topical keratolytics (salicylic acid, lactic acid, urea), topical and intralesional triamcinolone, intralesional fluorouracil, and surgical excision with skin grafting done have all been reported. Most recently, the combination of topical 1% cantharidin, 5% podophyllotoxin, and 30% salicyclic acid, applied under occlusion for 48 hours, was successful in a 15-year-old boy with a 10-year history of idiopathic KP. (2)

Dermatologists should not knuckle under the knowledge that only minimally effective treatments for KP exist — the dearth of efficacious options should serve a stimulus to learn more about KP pathogenesis to develop novel therapies.

Point to Remember: Knuckle pads, while benign, may be very irksome to patients. It is essential to differentiate primary from secondary KP. A further understanding of the pathogenesis of primary KP may lead to novel therapies.

Our Expert’s Viewpoint

Steven M. Purcell, DO
Chief, Division of Dermatology
Lehigh Valley Health Network

Dr. Heymann has expertly reviewed a common but vexing condition. We’ve all seen patients with knuckle pads but sometimes are at a loss as how to approach this condition. Dr. Heymann has outlined several treatment options reported in the literature. In the case we reported (reference #7) the patient responded nicely to daily treatment with 10% urea. For motivated patients, more aggressive approaches may be appropriate, such as utilizing the long pulsed Erbium:YAG laser. Ultimately, though, therapy must be tailored to the patient, but for now, the cornerstone of management is reassurance and doing no harm.

1. Hyman CH, Cohen PR. Report of a family with idiopathic knuckle padas and review of idiopathic and disease-associated knuckle pads. Dermatol Online J 2013; 15(5).

2. Hasbún C, Sandoval M, Curi M. A novel treatment of idiopathic knuckle pads with cantharidin-podphylotoxin-salicylic acid. Pediatr Dermatol 2019; 36: 544-545.

3. Mackey SL, Cobb MW. Knuckle pads. Cutis 1994; 54: 159-60.

4. Kelenjian S, Mattjie RA, Franz R, Biedermann T, Brockow K. Clinical features and management of superficial fibromatoses. J Dtsch Dermatol Ges 2019; 17: 393-397.

5. Weiss E, Amini S. A novel treatment for knuckle pads with intralesional fluorouracil. Arch Dermatol 2007; 143: 1458-1460.

6. Aslam F, Flug JA, Yonan Y, Noland SS. Erosive arthritis, fibromatosis, and keloids. A rare dermatoarthopathy. Case Rep Rheumatol 2018; Apr 22;2018:3893846.

7. Barrick C, Moran J, Oram C, Purcell S. Acrokeratoelastoidosis and knuckle pads coexisting in a child. Cutis 2018; 102: 344-346.

8. Mohamad J, Samuelov L, Ben-Amitai D, Machin N, et al. PLACK syndrome shows remarkable phenotypic homogeneity. Clin Exp Dermatol 2019; 44: 580-583.

9. Temel ŞG, Karakaş B, Şeker Ü, Turkgenç B, et al. A novel homozygous nonsense mutation in CAST associated with PLACK syndrome. Cell Tissue Res 2019; Aug 7 [Epub ahead of print].

10. Salam Kurtipek G, Kutlu O, Duran C, Kurku H, et al. Frequency of metabolic syndrome in patients with knuckle pads. J Dermatol 2015; 42: 1165-1168.