Collagenosis reactive perforating L87.1

Laugier and Woringer 1963; Mehregan et al. 1967.

Rare chronic skin disease characterized by transepidermal elimination of collagen and/or elastin through the skin. In the acquired (acquired collagenosis) form occurring in adults, it is often associated with diabetes mellitus and/or chronic terminal renal insufficiency.

Basically, there are 2 clinical syndromes:

• The much more frequent acquired reactive collagenosisin adults, which occurs mainly in diabetics and patients with renal insufficiency (incidences of up to 11% have been described). Acquired reactive collagenosis has also been described in patients with acute myeloid leukemia and after treatment with sorafenib.
• The very rare familial (primarily described as reactive perforating collagenosis), focal connective tissue degeneration with transepithelial shedding of collagen fibers, which already occurs in children. It can be assumed that this genodermatosis is identical to the"hyperkeratosis follicularis et parafollicularis in cutem penetrans" described by Kyrle.

1) Genodermatosis with unexplained etiopathogenesis.

2) Acquired in underlying diseases such as chronic terminal renal failure or diabetes mellitus. In isolated cases, the association with malignancies - prostate carcinoma, chronic lymphocytic leukemia - has been described (Huseynova L et al 2020).

3) Drug induced (e.g. by sorafenib - Vega Díez D et al. 2020).

The clinical picture has also been described in scabies and zoster, although the triggering of the disease in these cases is more likely to be reactive as a "Köbner phenomenon" with a corresponding disposition, or as an isotopic reaction.

Remark: probably as a result of mechanical or inflammatory irritation in receptive skin, there is focal damage to the collagenous connective tissue of the skin (scratching can experimentally induce RPK - Köbner phenomenon), which is finally discharged transepidermally.

Proteolytic enzymes such as matrix metalloproteases or serine proteases as well as modifications of sugar side chains on extracellular matrix proteins such as collagen I and III play an important role.

In classic reactive perforating collagenosis, the mean age of onset is 50-60 years. The average duration of disease is 8 months.

Mainly extensor sides of the extremities and the trunk. The face, palms of hands and soles of feet remain free of symptoms, as do the mucous membranes.

There is moderate to marked (non-histaminergic) pruritus.

Clinically, there are usually symmetrically distributed, few to numerous, disseminated or linearly grouped ( Köbner phenomenon), red, firm papules or plaques with central ulceration and hard, firmly adherent keratotic plug, initially about 0.2 cm in size, gradually increasing to 1.0 -2.0 cm in size.

Typically, there is evidence of a central crusty defect already in initial papules. After its detachment, an ulcerated crater is found, which heals spontaneously with hyperpigmentation after 2-4 weeks.

Remark: Although a rare disease, the clinical picture is unique and therefore unmistakable, so that the diagnosis is relatively easy to make if the clinical picture is known.

Hyperplastic epidermis with central bowl-shaped exulceration. In the material stored here, there are horny masses, granulation tissue with triggered, basophilic, collagenous fiber bundles (TOE stain). In the underlying dermis, a nonspecific mixed inflammatory infiltrate is seen.

Prurigo simplex subacuta (most important differential diagnosis); no causative underlying disease. Eminently severe itching of the scratched papules.

Prurigo nodularis (see below Prurigo chronic).

Rare differential diagnoses:

• Elastosis perforans serpiginosa (anular grouped papules with adherent keratoses).
• perforating granuloma anulare (skin-colored bifurcated papules)
• calcinosis cutis (rock-hard, pointed calcifications)
• Hyperkeratosis follicularis et parafollicularis in cutem penetrans (predominantly localized on the legs)
• Ecthyma (V.a. lower leg)

A causal therapy is otherwise not known. In the acquired forms, the treatment of the underlying disease is in the foreground (especially diabetes control!).

Externa: Highly potent corticoid externa or external retinoid (the sympt. Therapy with highly potent corticosteroids (also over large areas) has proved successful in our own experience and in the experience of some authors. Injections with depot steroids every 3 weeks are a good alternative, especially in areas of the back that are difficult to reach with cream.

Try PUVA therapy.

Alternative: Good experiences have been made with systemically administered allopurinol (100 mg/day/p.o.). The mechanism of action is unclear. It is possible that the inhibition of xanthine oxidase and an antioxidant effect inhibit the cross-linking of collagen fibers.

Alternative: Recently, several publications have been published describing good clinical results with dupilumab (Gil-Lianes J et al. 2022; Ying Y et al. 2022 )

Care: in addition to consistent skin care, it is advisable to cover the areas with a hydrocolloid plaster (dissolves the central plug, promotes healing, prevents scratching).

The acquired form of perforating collagenosis is known to have a relapsing course. There is a not inconsiderable tendency to heal spontaneously. It is important to treat the underlying disease (e.g. precise control of diabetes mellitus).

Perforations of the skin (perforating dermatoses) are found as a secondary phenomenon in a larger number of diseases.

For example: calcinosis cutis, foreign body granulomas, gout, chondrodermatitis nodularis chronica helicis, granuloma anulare, sarcoidosis, necrobiosis lipoidica, malignant melanoma, T-cell lymphoma, Paget's disease, Kyrle 's disease and others.

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