Case 1

A 47-year-old male presented to the dermatology OPD with burning pain and paresthesia over the right thoracic region for two months with a previous history of vesicular eruptions over the same site. On examination, there was a large, hyperpigmented, well-defined, irregular patch with satellite macules over T4-T5 dermatome extending from the midline chest to the spine (Fig. 1a). On close examination, multiple black open comedones were also present in the same region.

Figure 1: (a) Multiple comedones over post-inflammatory hyperpigmentation of healed herpes zoster. (b) Multiple keratin-filled, black, dilated follicular openings with a peripheral homogenous brown halo and a background reticular dark brown pigment network.

Case 2

A 35-year-old male, a diagnosed case of histoid leprosy, was on multibacillary multidrug therapy (MB-MDT). On his follow up visits, healed nodules of histoid leprosy appeared as oval anetodermic lesions studded with comedo-like lesions on his back (Fig. 2a).

Figure 2: (a) Healed nodules of histoid leprosy appearing as oval anetodermic lesions seen along with comedo-like lesions. (b and c) Black, keratin-filled, dilated, follicular openings on a brown homogenous background with loss of the pigment network. Shiny, wrinkled skin in non-polarized dermoscopy.

Case 3

A 27-year-old female presented with multiple swellings and brown pigmented spots. On examination, there were multiple neurofibromas, café-au-lait macules, a Lisch nodule in the left eye, positive crow’s sign, positive Patrick–Yesudian sign, and some neurofibromas with comedone-like lesions (Fig. 3a). Her son also presented with multiple café-au-lait macules and axillary freckling.

Figure 3: (a) Neurofibroma with comedo-like openings. (b and c) Black, dilated, oval, follicular opening with a surrounding translucent blackish halo seen over the nodular neurofibroma. “Double-ended pseudocomedone” on the scar of Cesarean section.

Case 4

A 32-year-old male, a renal transplant recipient, presented with multiple keratin plugs along the suture line of a closed arteriovenous fistula on his left forearm (Fig. 4a). He underwent the renal transplant three months earlier and developed these comedo-like lesions two months earlier.

Figure 4: (a) Keratin-filled pores along the suture line. (b) “Double-ended pseudocomedones” with a translucent, blackish halo in the overlying skin along the suture line.

Case 5

A 30-year-old female presented with a single asymptomatic keloidal scar with multiple open comedones in the center of her chest for the past three years (Fig. 5a).

Figure 5: Multiple open comedones over a keloid on the chest. (b) Central keratin plug with a peripheral, translucent, blackish halo, white dots interspersed with linear and arborizing telangiectasia on a brown background.

Case 6

A 30-year-old male presented with multiple open comedones in a curvilinear pattern over a healed patch of cellulitis on his left forearm (Fig. 6a). Comedo-like lesions developed within two weeks of healing of cellulitis.

Figure 6: (a) Multiple comedones in a curvilinear pattern on a healed patch of cellulitis. (b) Comedones with the “ring sign” interspersed with white structures indicating ongKoing fibrosis.

Case 7

A 78-year-old male presented with asymptomatic multiple open comedo-like openings on the face, chest, and scalp for the past year (Fig. 7a).

Figure 7: (a) Multiple open comedo-like openings on the chest and scalp. (b) Black, protuberant keratin plug (DBH), perifollicular rings, “double-ring” sign with linear and arborizing telangiectasia.

Table 1 lists the dermoscopic appearances of the above cases (Figs. 1b, 2b, 2c, 3b, 3c, 4b, 5b, 6b and 7b).

Table 1: Dermoscopic features of comedones in the described cases.

DISCUSSION

The immune response associated with comedogenesis primarily involves Th1 and Th17 cells. These T-helper cell subsets produce pro-inflammatory cytokines such as TNF-α, IL-1, IL-8, IL-12 and IL-17 [1]. There are only a few reports highlighting the dermoscopic appearances of comedones in association with other skin conditions.

Regarding case 1, the appearance of open comedones on a healed scar of herpes zoster (Fig. 1a) has been identified as an “isotopic response” by Wolf, or post-herpetic isotopic response (PHIR) [2]. Wolf’s isotopic response usually involves complete healing of herpes zoster or herpes simplex and the subsequent development of another unrelated skin disease at the same site. The pathophysiology behind this is hypothesized to be due to nerve damage and immune dysregulation by the virus. The most recent hypothesis involves locus minoris resistentiae due to a locally altered neuroimmune interaction. Locus minoris resistentiae refers to areas of the body more susceptible to disease due to reduced resistance, often following trauma or injury. Later, this vulnerability of healed lesions to develop distinct dysimmune reactions was referred to as the “immunocompromised cutaneous district” by Rucco et al. [3]. Varicella zoster virus infected dermatomes also fall under this entity, leading to the regional dysregulation of lymph flow and neuromediators. The release of neuropeptides, such as substance P, from damaged nerve endings may stimulate sebaceous gland lipogenesis, promoting the proliferation of Cutibacterium acnes and contributing to acne inflammation and comedone formation [4]. During herpes zoster healing, there is an upregulation of T-cell-mediated immunity, especially CD4+ and CD8+ T cells. These cells produce proinflammatory cytokines such as interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α), which stimulate Th1/Th17 immune response contributing to follicular hyperkeratinization and comedogenesis.

Regarding case 2, no previous case report has described a comedone-like lesion on the nodules or lesions of leprosy. In the lepromatous pole, the Th1 response is usually weaker and may lead to an increased Th2 or Th17 response, creating an immune imbalance. The dysregulation of immune pathways (Th17, TNF-α, IL-1) in both leprosy and comedogenesis create an environment conducive to the coexistence of both.

In case 3, comedones in the overlying skin could be attributed to the defective development of follicular ostia, leading to abnormal follicular induction and dysplasia [5]. Del Rio et al. described pilar dysplasia and folliculo-sebaceous in neurofibromatosis in two patients [6]. Epidermal follicular differentiation may occur in response to various dermal mesenchymal proliferations, such as dermatofibroma, scars, nevus sebaceous, and hemangiomas.

As for case 4, comedones may appear after mechanical damage to the follicular orifice after surgery or trauma. It may develop as a post-inflammatory phenomenon long after the damage. Healing wounds release pro-inflammatory cytokines such as TNF-α, IL-1, and IL-6, which promote follicular hyperkeratinization and comedogenesis. Suture sites may affect local sebaceous gland activity due to nerve damage or immune signaling, increasing sebum secretion and contributing to comedogenesis. Dermoscopic appearance shows the double-ended pseudocomedones (DEP) (Fig. 4b), which are typical of hidradenitis suppurativa. The new term “keratin-filled interconnected pores” is preferred due to the presence of two keratin-filled ends interconnected by a bluish-black tunnel beneath the translucent skin [7].

In case 5, chronic inflammation in a keloid will contribute to sebum production and keratinocyte proliferation leading to comedone formation [8]. The thickened, fibrotic nature of keloidal tissue reduces the skin’s elasticity and ability to expel sebum effectively. The presence of comedones in a keloid will show stronger sebaceous gland activity that may favor a good response after isotretinoin therapy.

In case 6, inflammatory mediators after cellulitis may disrupt the sebaceous glands and lead to the accumulation of sebum and keratin, resulting in comedone formation. Even after cellulitis heals, residual bacteria or changes in the skin’s microbiome may lead to blocked hair follicles and comedone formation. These may be considered “tombstone” comedones similar to those observed in healed scars of hidradenitis suppurativa [9]. This is a marker of severe inflammation.

Case 7 represents widespread trichostasis spinulosa, a follicular disorder with the retention of numerous telogen hairs within sebaceous follicles that may have the appearance of open comedones. It is mostly seen in the elderly with a male-to-female ratio of 1:2. Hyperkeratosis in the follicular infundibulum obstructs normal hair shedding. Widespread distribution in our case may have been due to the use of occlusive substances such as oils on the skin, repeated friction, and tight-fitting clothes. Predominant seborrheic distribution points toward the chronic oil application resulting in follicular obstruction. Dermoscopic findings include follicular hyperkeratosis, dermoscopic blackhead-like structure (DBH), hair tuft, “circle hair,” and “rolled hair” [10]. Here, we noticed a central keratin plug in dilated hair follicles, DBH, and circle hair, or the “double-ring sign” (Fig. 7b).

The presence of comedones in these conditions likely resulted from follicular occlusion, either due to dermal infiltration (as in neurofibromatosis and histoid leprosy) or post-inflammatory changes (as in herpes zoster and surgical scars). The ICD (immunocompromised cutaneous district) theory proposed by Rucco may also explain the presence of comedones in leprosy, neurofibromatosis, suture sites, keloids, and post-cellulitis scars along with post herpes zoster, as the altered skin microenvironment and reduced immune defense might promote comedogenesis.

CONCLUSION

Localized immune dysregulation at these sites may create conditions conducive to secondary phenomena such as comedones. Conditions like trichostasis spinulosa involve inherent abnormalities of the hair follicle, leading to comedonal formation. The ICD theory explains the susceptibility of certain areas to comedogenesis due to disrupted neuroimmune interactions or reduced skin resilience. This case series highlights the distinct atypical patterns of comedones and their immunopathogenesis. These insights not only aid in accurate diagnosis but also deepen our comprehension of the interplay between localized immune dysregulation and follicular abnormalities. Such knowledge is essential for optimizing management strategies and guiding further research into these uncommon dermatological phenomena.