Granulomatosis disciformis in a non-diabetic patient^*

Dear Editor,

Miescher's Granulomatosis (also known as granulomatosis disciformis chronica et progressiva) (GDML) is a chronic disease of unknown etiology, with clinical characteristics that are quite similar to lipoidic necrobiosis (LN) but that differ from this disease due to its anatomopathologic characteristics. In GDML, one can generally observe an exuberant granulomatous reaction, comprised of epithelioid cells, with gigantocytes and plasmocytes, and without necrosis, whereas in the LN, one can observe palisading granulomas with necrobiosis.^1,2

Few studies have reported on this disease in the literature; however, it is believed that GDML is more commonly found in middle-aged women. Initially, it was proposed that the core difference between GDML and LN was the fact that the former was not associated with diabetes mellitus, with only LN associated to this condition. However, this theory was proven to be unfounded, as it was discovered that both diseases can be associated or not with diabetes mellitus.^1,2,3

In the present case, a 46-year-old female patient reported the appearance of annular lesions on her forearms and legs over the past three years, with local yet discreet pruritis. The patient presented systemic arterial hypertension, which was treated with propranolol, and the patient denied any prior diagnosis of diabetes mellitus. Upon physical examination, it was possible to observe annular erythematous plaques, with infiltrated edges, together with an atrophic and telangiectatic center, with a yellowish color and an aspect of cigarette paper when wrinkled (Figure 1 and 2). The initial hypothetical diagnosis was of LN, and a biopsy of a lesion on the right forearm was, therefore, performed. The anatomopathologic exam showed a perivascular and interstitial inflammatory infiltrate, comprised of lymphocytes, plasmocytes, and epithelioid macrophages, with the presence of Langhans multinucleated giant cells and thick collagen fibers (Figure 3). The biopsy proved to be compatible with the diagnosis of GDML. Laboratory exams were also requested to investigate the lipid profile and the change in the glycemic curve, which presented no changes. The patient began her treatment with sulfone, administered orally, and topical clobetasol presenting, to date, partial regression of the lesions.

Figure 1
Annular erythematous plaques, with infiltrated edges and a yellowish, atrophic, and telangiectatic center on the legs

Figure 2
Lesion with an aspect of “cigarette paper” when wrinkled

Figure 3
Sclerotic dermis, with tuberculoid granuloma and dense perivascular lymphoplasmacytic component (Hematoxylin & eosin x100)

GDML was described for the first time by Miescher and Leder in 1948. The authors illustrated great clinical similarities of this entity with LN, a chronic disease of unknown origin but that presented distinct histopathological characteristics.²

By contrast, other authors, such as Ringrose et al.,⁴ believed that GDML was a non-diabetic variant of LN. Later, however, it was shown that many of the GDML patients were in fact pre-diabetics or presented change in their glucose curves, proving that both co-morbidities can be concomitant.¹

The etiology, of both LN and GDML, is still rather unknown. It is believed that changes in the small blood vessels of the skin and hypodermis are important in their pathogeneses, and that habits, like smoking, can worsen vascular damage or even precipitate the clinical manifestation of the disease. The amount of smoking and the beginning of the smoking habit are important risk factors for the development of GDML. Other factors include venous stasis, genetic predisposition, and trauma.⁴

Clinically, GDML can also be confused with LN. The lesions are normally bilateral and symmetric on the anterior surface of the lower and upper limbs, slightly yellow, of a firm consistency, of a translucent and shiny surface, with a discretely atrophic center and subtly raised edges.^1,2,3

From the histopathological point of view, GDML joins the following aspects that differentiate it from LN. First, the intense participation of the hypodermis can be observed in specific cases, together with a larger quantity of plasmocytes in the site; a minimal degree of necrobiosis; an area of hyalinization of collagen; and the absence or lack of mucin deposits. By contrast, in the LM, one can almost always observe the presence of "palisading granulomas" with necrobiosis.^1,2,3

The treatment for LN and GDML is difficult to determine, as strong topical corticosteroids, systemic corticosteroids, pentoxifylline, puva therapy, mycophenolate mofetil, chloroquine, sulfone, and anti-TNFs can all be used. It is important to highlight that one of the main long-term risks of NL is its transformation in squamous cell carcinoma.⁵

The present case reported on a middle-aged, non-diabetic female patient who had reported the appearance of lesions on her limbs three years three years before. The clinical condition of this case was very similar to that of LN, and the diagnosis of the disease was only able to be confirmed by performing an anatomopathologic exam that was compatible with GDML.

It is important to note that, due to its rarity and its morphological similarity to LN, GDML is subject to being clinically underdiagnosed, and a biopsy should always be performed to confirm a proper histopathological diagnosis.

• *
  Work conducted at Santo Amaro University, São Paulo, SP, Brazil.
• Financial support: None.

REFERENCES

• ¹
  Proença NG, Pereira JM, Muller H. Granulomatose disciforme crônica e progressiva de Miescher e Leder, uma variedade da necrobiose lipoídica diabeticorum. An Bras Dermatol. 1976; 51:239-50.
• ²
  Chiale GF, Serra M. La granulomatosi disciforme cronica e progressiva de Miescher e Leder. G Ital Dermatol Minerva Dermatol. 1971;46:304-9.
• ³
  Rabello FE, Mendes LR, Marques AS. Granulomatose disciforme (Miescher 1936-1948) e sua discutida nosologia. Rev Argent Dermatol.1982;63:237-47.
• ⁴
  Ringrose EJ. Smoking, necrobiosis lipoidica, granulomatosis disciformis chronica progressiva. AMA Arch Derm. 1959;79:635-40.
• ⁵
  Bergler-Czop B, Brzezinska-Wcislo L, Rogala-Poborska I. Miescher's granulomatosis (granulomatosis disciformis chronica et progressiva) in a non-diabetic patient - case report. Diagn Pathol. 2009;4:28.

Publication Dates

• Publication in this collection
  May-Jun 2017

History

• Received
  04 Mar 2016
• Accepted
  17 Oct 2016