Cobblestone Appearances in Dermatology : Clinical Dermatology Review (2024)

Introduction

It is an old perception among medical practitioners that diagnosis is difficult in dermatology. There are many factors, other than the experience of the examining dermatologist, which justify the above statement and responsible for diagnostic fallacy. They are color of the skin, age and immune status of the patient, duration of the skin lesion, prior use of any medicine, and wide morphologic spectrum of dermatologic conditions. Certain dermatosis may simulate the clinical picture of other dermatoses. On the bright side, there are few morphologic lesions or patterns which are so characteristic that, in corroboration with history and other clinical findings, diagnosis becomes easier. “Cobblestone” is one such example which is used to describe a characteristic morphologic pattern of some dermatoses. This term implies a three-dimensional visual appearance of multiple, equally sized, round, raised lesions resembling roads paved by multiple equal-sized “cobbled” stones [Figure 1]. It can be observed both clinically and dermoscopically. After searching databases of PubMed, Medline, Scopus, Embase, and Web of Science, dermatoses with cobblestone appearance (both clinical and dermoscopic) are compiled in Table 1. Cobblestone skin lesions are further subdivided into groups based on their lesions as shown in Table 2. For the ease of reading, all the conditions are arranged in alphabetical order.

1. Acrokeratosis verruciformis of Hopf: The classic lesions are flat-topped, hyperkeratotic, skin-colored papules on the dorsal aspect of the hands and forearms [Figure 2]. On dermoscopy, it shows irregular, white, hom*ogenous areas and cobblestone appearances[¹]
2. Bullous congenital ichthyosiform erythroderma (BCIE): Erythematous and bullous lesions of BCIE usually disappear in few months after birth and convert into ichthyotic, hyperkeratotic brown scaly lesions, and cobblestone-like keratosis on extensor surfaces such as the dorsal hands and feet[²]
3. Cheilitis granulomatosa (also known as Miescher's cheilitis): It is a rare, idiopathic, chronic, persistent, painless, granulomatous swelling of the lips of uncertain etiology, though strongly related to Crohn's disease, sarcoidosis, and allergy. In this condition, labial mucosa gets thickened and folded like cobblestone with or without facial swelling[³]
4. Congenital erosive and vesicular dermatosis: It characteristically heals with symmetrical reticulated supple scarring. These scars are slightly hyperpigmented and cobblestone-like especially on the forehead and scalp[⁴]
5. Congenital melanocytic nevus (CMN): Surface irregularities such as nodular changes and mammillations are commonly seen in CMN [Figure 3]. On dermoscopy, a globular or cobblestone pattern is also observed.[⁵] Cobblestone pattern is a variation of the globular pattern, seen as larger, closely aggregated, and brown-gray globule-like structures (correspond to nevomelanocytic nests in the dermis)
6. Connective tissue nevus: Collagenoma can present as multiple skin-colored papules and plaques in cobblestone pattern [Figures 4 and 5]. In a single case, the dermoscopic examination of shagreen patch also revealed this pattern[⁶]
7. Cowden's syndrome: It is a multiple hamartoma syndrome which affects many organs such as the thyroid, breast, brain, eyes, skin, intestines, and genitourinary tract. Patients develop many distinct mucocutaneous manifestations ranging from skin-colored coalescing lichenoid papules around the eyes and mouth to sclerotic fibromas. Of note, lingual, gingival, and buccal mucosa develop cobblestone or warty lesions[⁷]
8. Darier disease: White cobblestone papules with central depression on the buccal mucosa and palate are very characteristic in Darier disease [Figure 6]. Gingiva and tongue may also get involved. Lesions on the hard palate may simulate nicotinic stomatitis[⁸]
9. Elephantiasis nostras verrucosa: It is a rare presentation of chronic lymphedema of the lower limb arising due to various factors affecting their lymphatic drainage. It often manifests as nonpitting edema and hyperkeratotic or verrucous papules and nodules with cobblestone-like appearance [Figure 7][⁹]
10. Eosinophilic fasciitis (also known as Shulman's syndrome): It is a rare autoimmune pseudosclerodermic condition which starts with acute painful tender swelling in distal extremities and later becomes indurated due to dermal and subdermal fibrosis. Peau d' orange or cobblestone appearance of hyperpigmented skin with venous furrowing along veins (groove sign) are evocative findings[¹⁰]
11. Erythropoietic protoporphyria (EPP): Blistering lesions of EPP on knuckles and fingers may heal with waxy and cobblestone-like induration[¹¹]
12. Glomuvenous malformation: It is caused by loss-of-function mutations in the GLMN gene, clinically characterized by multiple, painful, bluish-purple, hyperkeratotic nodules and plaques on extremities. These plaques are like cobblestone and noncompressible[¹²]
13. Hystrix-like ichthyosis with deafness syndrome: Hyperkeratosis is more extensive, prominent, and cobblestone-like, often preceded by erythroderma[¹³]
14. Herpes zoster: The classic grouped cutaneous vesicles of herpes zoster may also have cobblestone surface which are always inflamed and erythematous [Figure 8][¹⁴]
15. Ichthyosis hystrix: Porcupine-like spiny papules and/or cobblestone plaques over large joints are diagnostic features of this condition. Palms and soles are spared in its nail-patella syndrome phenotype[¹⁵]
16. Keratitis-ichthyosis-deafness syndrome: It presents as mildly erythematous, irregular cobblestone-like hyperkeratosis on extensors and face[¹³]
17. Lichen myxedematosus: It is also known as papular mucinosis and clinically characterized by multiple, shiny, waxy, skin-colored, small, dome-shaped, firm papules coalescing to form plaques, sometimes giving a cobblestone appearance [Figure 9][¹⁶]
18. Lipoid proteinosis (Urbach–Wiethe disease): Cobblestone appearance of oral mucosa due to hyaline deposits in the form of infiltrative yellowish papules is a common finding in this deposition disorder[¹⁷]
19. Morphea profunda: Typically presents with bound-down, subcutaneous atrophic plaques give cobblestone feel[¹⁸]
20. Multicentric reticulohistiocytosis: It is a multisystem disorder of histiocytic proliferation affecting the skin, joints, and viscera. The cutaneous lesions are characterized by round, translucent, and reddish-brown papules often coalescing into plaques giving a cobblestone appearance [Figure 10],[Figure 11], [Figure 12][¹⁹]
21. Nephrogenic systemic fibrosis: A rare but serious condition caused by gadolinium exposure in patients with renal failure. It is characterized by generalized skin fibrosis predominantly affecting the limbs and trunk. Hyperpigmented fibrotic indurated plaques with cobblestone or woody appearance are very common[²⁰]
22. Nevus sebaceous of Jadassohn: Linear or round, yellowish, cobblestone-like hairless solitary plaque on the scalp is quite diagnostic [Figure 13]. It also shows a cobblestone pattern of yellowish globules on dermoscopy[²¹]
23. Port-wine stain: It is seen at birth as irregular, reddish/purple macules which, with age, develop cobblestone-like hypertrophic papular/nodular lesions[²²]
24. Postvitiligo grafting: Cobblestoning is one of the common complications of punch grafting for vitiligo [Figure 14]
25. Pseudoxanthoma elasticum: It is a rare genetic disease of ectopic calcification and fragmentation of elastic fibers, clinically manifested by small yellowish papules on wrinkled skin of flexures (commonly on side of the neck, axillae, groins, and abdomen) [Figure 15]. These papules may coalesce and look like cobblestone, Moroccan leather, or chicken skin[²³]
26. Systemic sclerosis: Cobblestone appearance of the skin and mucosa is uncommon in systemic sclerosis. On the skin, it is seen as shiny papules due to lymphatic obstruction by fibrosis.[²⁴] The esophageal epithelium also looks like cobblestone because of pearly white plaques
27. Tufted angioma: It often presents with a large erythematous plaque on the trunk with a cobblestone surface[²⁵]
28. Vernal conjunctivitis: Cobblestoning of the upper eyelid conjunctiva is a frequent finding in vernal conjunctivitis due to papillary hypertrophy[²⁶]
29. Verrucous epidermal nevus: Its dermoscopic features include large brown circles surrounding a hypopigmented area, fissures, comedo-like openings, milia-like cysts, brown globules and dots, papillomatous surface, and cobblestone appearance.[²⁷]

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REFERENCES